Hubbry Logo
BiochemistryBiochemistryMain
Open search
Biochemistry
Community hub
Biochemistry
logo
8 pages, 0 posts
0 subscribers
Be the first to start a discussion here.
Be the first to start a discussion here.
Biochemistry
Biochemistry
Biochemistry
View on Wikipedia
from Wikipedia
Part of a series on
Biochemistry
Key components
List of biochemists
Biomolecule families
Chemical synthesis
Biochemistry fields
Glossaries

Biochemistry, or biological chemistry, is the study of chemical processes within and relating to living organisms.[1] A sub-discipline of both chemistry and biology, biochemistry may be divided into three fields: structural biology, enzymology, and metabolism. Over the last decades of the 20th century, biochemistry has become successful at explaining living processes through these three disciplines. Almost all areas of the life sciences are being uncovered and developed through biochemical methodology and research.[2] Biochemistry focuses on understanding the chemical basis that allows biological molecules to give rise to the processes that occur within living cells and between cells,[3] in turn relating greatly to the understanding of tissues and organs as well as organism structure and function.[4] Biochemistry is closely related to molecular biology, the study of the molecular mechanisms of biological phenomena.[5]

Much of biochemistry deals with the structures, functions, and interactions of biological macromolecules such as proteins, nucleic acids, carbohydrates, and lipids. They provide the structure of cells and perform many of the functions associated with life.[6] The chemistry of the cell also depends upon the reactions of small molecules and ions. These can be inorganic (for example, water and metal ions) or organic (for example, the amino acids, which are used to synthesize proteins).[7] The mechanisms used by cells to harness energy from their environment via chemical reactions are known as metabolism. The findings of biochemistry are applied primarily in medicine, nutrition, and agriculture. In medicine, biochemists investigate the causes and cures of diseases.[8] Nutrition studies how to maintain health and wellness and also the effects of nutritional deficiencies.[9] In agriculture, biochemists investigate soil and fertilizers with the goal of improving crop cultivation, crop storage, and pest control. In recent decades, biochemical principles and methods have been combined with problem-solving approaches from engineering to manipulate living systems in order to produce useful tools for research, industrial processes, and diagnosis and control of disease—the discipline of biotechnology.

History

[edit]
Main article: History of biochemistry
Gerty Cori and Carl Cori jointly won the Nobel Prize in 1947 for their discovery of the Cori cycle at RPMI.

At its most comprehensive definition, biochemistry can be seen as a study of the components and composition of living things and how they come together to become life. In this sense, the history of biochemistry may therefore go back as far as the ancient Greeks.[10] However, biochemistry as a specific scientific discipline began sometime in the 19th century, or a little earlier, depending on which aspect of biochemistry is being focused on. Some argued that the beginning of biochemistry may have been the discovery of the first enzyme, diastase (now called amylase), in 1833 by Anselme Payen,[11] while others considered Eduard Buchner's first demonstration of a complex biochemical process alcoholic fermentation in cell-free extracts in 1897 to be the birth of biochemistry.[12][13] Some might also point as its beginning to the influential 1842 work by Justus von Liebig, Animal chemistry, or, Organic chemistry in its applications to physiology and pathology, which presented a chemical theory of metabolism,[10] or even earlier to the 18th century studies on fermentation and respiration by Antoine Lavoisier.[14][15] Many other pioneers in the field who helped to uncover the layers of complexity of biochemistry have been proclaimed founders of modern biochemistry. Emil Fischer, who studied the chemistry of proteins,[16] and F. Gowland Hopkins, who studied enzymes and the dynamic nature of biochemistry, represent two examples of early biochemists.[17]

The term "biochemistry" was first used when Vinzenz Kletzinsky (1826–1882) had his "Compendium der Biochemie" printed in Vienna in 1858; it derived from a combination of biology and chemistry. In 1877, Felix Hoppe-Seyler used the term (biochemie in German) as a synonym for physiological chemistry in the foreword to the first issue of Zeitschrift für Physiologische Chemie (Journal of Physiological Chemistry) where he argued for the setting up of institutes dedicated to this field of study.[18][19] The German chemist Carl Neuberg however is often cited to have coined the word in 1903,[20][21][22] while some credited it to Franz Hofmeister.[23]

DNA structure (1D65​)[24]

It was once generally believed that life and its materials had some essential property or substance (often referred to as the "vital principle") distinct from any found in non-living matter, and it was thought that only living beings could produce the molecules of life.[25] In 1828, Friedrich Wöhler published a paper on his serendipitous urea synthesis from potassium cyanate and ammonium sulfate; some regarded that as a direct overthrow of vitalism and the establishment of organic chemistry.[26][27] However, the Wöhler synthesis has sparked controversy as some reject the death of vitalism at his hands.[28] Since then, biochemistry has advanced, especially since the mid-20th century, with the development of new techniques such as chromatography, X-ray diffraction, dual polarisation interferometry, NMR spectroscopy, radioisotopic labeling, electron microscopy and molecular dynamics simulations. These techniques allowed for the discovery and detailed analysis of many molecules and metabolic pathways of the cell, such as glycolysis and the Krebs cycle (citric acid cycle), and led to an understanding of biochemistry on a molecular level.[citation needed]

Another significant historic event in biochemistry is the discovery of the gene, and its role in the transfer of information in the cell. In the 1950s, James D. Watson, Francis Crick, Rosalind Franklin and Maurice Wilkins were instrumental in solving DNA structure and suggesting its relationship with the genetic transfer of information.[29] In 1958, George Beadle and Edward Tatum received the Nobel Prize for work in fungi showing that one gene produces one enzyme.[30] In 1988, Colin Pitchfork was the first person convicted of murder with DNA evidence, which led to the growth of forensic science.[31] More recently, Andrew Z. Fire and Craig C. Mello received the 2006 Nobel Prize for discovering the role of RNA interference (RNAi) in the silencing of gene expression.[32]

Starting materials: the chemical elements of life

[edit]
The main elements that compose the human body shown from most abundant (by mass) to least abundant
Main articles: Composition of the human body and Dietary mineral

Around two dozen chemical elements are essential to various kinds of biological life. Most rare elements on Earth are not needed by life (exceptions being selenium and iodine),[33] while a few common ones (aluminium and titanium) are not used. Most organisms share element needs, but there are a few differences between plants and animals. For example, ocean algae use bromine, but land plants and animals do not seem to need any. All animals require sodium, but is not an essential element for plants. Plants need boron and silicon, but animals may not (or may need ultra-small amounts).[34]

Just six elements—carbon, hydrogen, nitrogen, oxygen, calcium and phosphorus—make up almost 99% of the mass of living cells, including those in the human body (see composition of the human body for a complete list). In addition to the six major elements that compose most of the human body, humans require smaller amounts of possibly 18 more.[35]

Biomolecules

[edit]
Main article: Biomolecule

The 4 main classes of molecules in biochemistry (often called biomolecules) are carbohydrates, lipids, proteins, and nucleic acids.[36] Many biological molecules are polymers: in this terminology, monomers are relatively small macromolecules that are linked together to create large macromolecules known as polymers. When monomers are linked together to synthesize a biological polymer, they undergo a process called dehydration synthesis. Different macromolecules can assemble in larger complexes, often needed for biological activity.

Carbohydrates

[edit]
Main articles: Carbohydrate, Monosaccharide, Disaccharide, and Polysaccharide
Carbohydrates
Glucose, a monosaccharide
A molecule of sucrose (glucose + fructose), a disaccharide
Amylose, a polysaccharide made up of several thousand glucose units

Two of the main functions of carbohydrates are energy storage and providing structure. One of the common sugars known as glucose is a carbohydrate, but not all carbohydrates are sugars. There are more carbohydrates on Earth than any other known type of biomolecule; they are used to store energy and genetic information, as well as play important roles in cell to cell interactions and communications.[citation needed]

The simplest type of carbohydrate is a monosaccharide, which among other properties contains carbon, hydrogen, and oxygen, mostly in a ratio of 1:2:1 (generalized formula CnH2nOn, where n is at least 3). Glucose (C6H12O6) is one of the most important carbohydrates; others include fructose (C6H12O6), the sugar commonly associated with the sweet taste of fruits,[37][a] and deoxyribose (C5H10O4), a component of DNA. A monosaccharide can switch between acyclic (open-chain) form and a cyclic form. The open-chain form can be turned into a ring of carbon atoms bridged by an oxygen atom created from the carbonyl group of one end and the hydroxyl group of another. The cyclic molecule has a hemiacetal or hemiketal group, depending on whether the linear form was an aldose or a ketose.[39]

In these cyclic forms, the ring usually has 5 or 6 atoms. These forms are called furanoses and pyranoses, respectively—by analogy with furan and pyran, the simplest compounds with the same carbon-oxygen ring (although they lack the carbon-carbon double bonds of these two molecules). For example, the aldohexose glucose may form a hemiacetal linkage between the hydroxyl on carbon 1 and the oxygen on carbon 4, yielding a molecule with a 5-membered ring, called glucofuranose. The same reaction can take place between carbons 1 and 5 to form a molecule with a 6-membered ring, called glucopyranose. Cyclic forms with a 7-atom ring called heptoses are rare.[citation needed]

Two monosaccharides can be joined by a glycosidic or ester bond into a disaccharide through a dehydration reaction during which a molecule of water is released. The reverse reaction in which the glycosidic bond of a disaccharide is broken into two monosaccharides is termed hydrolysis. The best-known disaccharide is sucrose or ordinary sugar, which consists of a glucose molecule and a fructose molecule joined. Another important disaccharide is lactose found in milk, consisting of a glucose molecule and a galactose molecule. Lactose may be hydrolysed by lactase, and deficiency in this enzyme results in lactose intolerance.

When a few (around three to six) monosaccharides are joined, it is called an oligosaccharide (oligo- meaning "few"). These molecules tend to be used as markers and signals, as well as having some other uses.[40] Many monosaccharides joined form a polysaccharide. They can be joined in one long linear chain, or they may be branched. Two of the most common polysaccharides are cellulose and glycogen, both consisting of repeating glucose monomers. Cellulose is an important structural component of plant's cell walls and glycogen is used as a form of energy storage in animals.

Sugar can be characterized by having reducing or non-reducing ends. A reducing end of a carbohydrate is a carbon atom that can be in equilibrium with the open-chain aldehyde (aldose) or keto form (ketose). If the joining of monomers takes place at such a carbon atom, the free hydroxy group of the pyranose or furanose form is exchanged with an OH-side-chain of another sugar, yielding a full acetal. This prevents opening of the chain to the aldehyde or keto form and renders the modified residue non-reducing. Lactose contains a reducing end at its glucose moiety, whereas the galactose moiety forms a full acetal with the C4-OH group of glucose. Saccharose does not have a reducing end because of full acetal formation between the aldehyde carbon of glucose (C1) and the keto carbon of fructose (C2).

Lipids

[edit]
Main articles: Lipid, Glycerol, and Fatty acid
Structures of some common lipids. At the top are cholesterol and oleic acid.[41] The middle structure is a triglyceride composed of oleoyl, stearoyl, and palmitoyl chains attached to a glycerol backbone. At the bottom is the common phospholipid, phosphatidylcholine.[42]

Lipids comprise a diverse range of molecules and to some extent is a catchall for relatively water-insoluble or nonpolar compounds of biological origin, including waxes, fatty acids, fatty-acid derived phospholipids, sphingolipids, glycolipids, and terpenoids (e.g., retinoids and steroids). Some lipids are linear, open-chain aliphatic molecules, while others have ring structures. Some are aromatic (with a cyclic [ring] and planar [flat] structure) while others are not. Some are flexible, while others are rigid.[43]

Lipids are usually made from one molecule of glycerol combined with other molecules. In triglycerides, the main group of bulk lipids, there is one molecule of glycerol and three fatty acids. Fatty acids are considered the monomer in that case, and may be saturated (no double bonds in the carbon chain) or unsaturated (one or more double bonds in the carbon chain).[citation needed]

Most lipids have some polar character and are largely nonpolar. In general, the bulk of their structure is nonpolar or hydrophobic ("water-fearing"), meaning that it does not interact well with polar solvents like water. Another part of their structure is polar or hydrophilic ("water-loving") and will tend to associate with polar solvents like water. This makes them amphiphilic molecules (having both hydrophobic and hydrophilic portions). In the case of cholesterol, the polar group is a mere –OH (hydroxyl or alcohol).[44]

In the case of phospholipids, the polar groups are considerably larger and more polar, as described below.

Lipids are an integral part of our daily diet. Most oils and milk products that we use for cooking and eating like butter, cheese, ghee etc. are composed of fats. Vegetable oils are rich in various polyunsaturated fatty acids (PUFA). Lipid-containing foods undergo digestion within the body and are broken into fatty acids and glycerol, the final degradation products of fats and lipids. Lipids, especially phospholipids, are also used in various pharmaceutical products, either as co-solubilizers (e.g. in parenteral infusions) or else as drug carrier components (e.g. in a liposome or transfersome).

Proteins

[edit]
Main articles: Protein and Amino acid
The general structure of an α-amino acid, with the amino group on the left and the carboxyl group on the right

Proteins are very large molecules—macro-biopolymers—made from monomers called amino acids. An amino acid consists of an alpha carbon atom attached to an amino group, –NH2, a carboxylic acid group, –COOH (although these exist as –NH3+ and –COO− under physiologic conditions), a simple hydrogen atom, and a side chain commonly denoted as "–R". The side chain "R" is different for each amino acid of which there are 20 standard ones. It is this "R" group that makes each amino acid different, and the properties of the side chains greatly influence the overall three-dimensional conformation of a protein. Some amino acids have functions by themselves or in a modified form; for instance, glutamate functions as an important neurotransmitter. Amino acids can be joined via a peptide bond. In this dehydration synthesis, a water molecule is removed and the peptide bond connects the nitrogen of one amino acid's amino group to the carbon of the other's carboxylic acid group. The resulting molecule is called a dipeptide, and short stretches of amino acids (usually, fewer than thirty) are called peptides or polypeptides. Longer stretches merit the title proteins. As an example, the important blood serum protein albumin contains 585 amino acid residues.[45]

Generic amino acids (1) in neutral form, (2) as they exist physiologically, and (3) joined as a dipeptide
A schematic of hemoglobin. The red and blue ribbons represent the protein globin; the green structures are the heme groups.

Proteins can have structural and/or functional roles. For instance, movements of the proteins actin and myosin ultimately are responsible for the contraction of skeletal muscle. One property many proteins have is that they specifically bind to a certain molecule or class of molecules—they may be extremely selective in what they bind. Antibodies are an example of proteins that attach to one specific type of molecule. Antibodies are composed of heavy and light chains. Two heavy chains would be linked to two light chains through disulfide linkages between their amino acids. Antibodies are specific through variation based on differences in the N-terminal domain.[46]

The enzyme-linked immunosorbent assay (ELISA), which uses antibodies, is one of the most sensitive tests modern medicine uses to detect various biomolecules. Probably the most important proteins, however, are the enzymes. Virtually every reaction in a living cell requires an enzyme to lower the activation energy of the reaction. These molecules recognize specific reactant molecules called substrates; they then catalyze the reaction between them. By lowering the activation energy, the enzyme speeds up that reaction by a rate of 1011 or more; a reaction that would normally take over 3,000 years to complete spontaneously might take less than a second with an enzyme. The enzyme itself is not used up in the process and is free to catalyze the same reaction with a new set of substrates. Using various modifiers, the activity of the enzyme can be regulated, enabling control of the biochemistry of the cell as a whole.

The structure of proteins is traditionally described in a hierarchy of four levels. The primary structure of a protein consists of its linear sequence of amino acids; for instance, "alanine-glycine-tryptophan-serine-glutamate-asparagine-glycine-lysine-...". Secondary structure is concerned with local morphology (morphology being the study of structure). Some combinations of amino acids will tend to curl up in a coil called an α-helix or into a sheet called a β-sheet; some α-helixes can be seen in the hemoglobin schematic above. Tertiary structure is the entire three-dimensional shape of the protein. This shape is determined by the sequence of amino acids. In fact, a single change can change the entire structure. The alpha chain of hemoglobin contains 146 amino acid residues; substitution of the glutamate residue at position 6 with a valine residue changes the behavior of hemoglobin so much that it results in sickle-cell disease. Finally, quaternary structure is concerned with the structure of a protein with multiple peptide subunits, like hemoglobin with its four subunits. Not all proteins have more than one subunit.[47]

Examples of protein structures from the Protein Data Bank
Members of a protein family, as represented by the structures of the isomerase domains

Ingested proteins are usually broken up into single amino acids or dipeptides in the small intestine and then absorbed. They can then be joined to form new proteins. Intermediate products of glycolysis, the citric acid cycle, and the pentose phosphate pathway can be used to form all twenty amino acids, and most bacteria and plants possess all the necessary enzymes to synthesize them. Humans and other mammals, however, can synthesize only half of them. They cannot synthesize isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. Because they must be ingested, these are the essential amino acids. Mammals do possess the enzymes to synthesize alanine, asparagine, aspartate, cysteine, glutamate, glutamine, glycine, proline, serine, and tyrosine, the nonessential amino acids. While they can synthesize arginine and histidine, they cannot produce it in sufficient amounts for young, growing animals, and so these are often considered essential amino acids.

If the amino group is removed from an amino acid, it leaves behind a carbon skeleton called an α-keto acid. Enzymes called transaminases can easily transfer the amino group from one amino acid (making it an α-keto acid) to another α-keto acid (making it an amino acid). This is important in the biosynthesis of amino acids, as for many of the pathways, intermediates from other biochemical pathways are converted to the α-keto acid skeleton, and then an amino group is added, often via transamination. The amino acids may then be linked together to form a protein.

A similar process is used to break down proteins. It is first hydrolyzed into its component amino acids. Free ammonia (NH3), existing as the ammonium ion (NH4+) in blood, is toxic to life forms. A suitable method for excreting it must therefore exist. Different tactics have evolved in different animals, depending on the animals' needs. Unicellular organisms release the ammonia into the environment. Likewise, bony fish can release ammonia into the water where it is quickly diluted. In general, mammals convert ammonia into urea, via the urea cycle.

In order to determine whether two proteins are related, or in other words to decide whether they are homologous or not, scientists use sequence-comparison methods. Methods like sequence alignments and structural alignments are powerful tools that help scientists identify homologies between related molecules. The relevance of finding homologies among proteins goes beyond forming an evolutionary pattern of protein families. By finding how similar two protein sequences are, we acquire knowledge about their structure and therefore their function.

Nucleic acids

[edit]
Main articles: Nucleic acid, DNA, RNA, and Nucleotide
The structure of deoxyribonucleic acid (DNA); the picture shows the monomers being put together.

Nucleic acids, so-called because of their prevalence in cellular nuclei, is the generic name of the family of biopolymers. They are complex, high-molecular-weight biochemical macromolecules that can convey genetic information in all living cells and viruses.[2] The monomers are called nucleotides, and each consists of three components: a nitrogenous heterocyclic base (either a purine or a pyrimidine), a pentose sugar, and a phosphate group.[48]

Structural elements of common nucleic acid constituents. Because they contain at least one phosphate group, the compounds marked nucleoside monophosphate, nucleoside diphosphate and nucleoside triphosphate are all nucleotides (not phosphate-lacking nucleosides).

The most common nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). The phosphate group and the sugar of each nucleotide bond with each other to form the backbone of the nucleic acid, while the sequence of nitrogenous bases stores the information. The most common nitrogenous bases are adenine, cytosine, guanine, thymine, and uracil. The nitrogenous bases of each strand of a nucleic acid will form hydrogen bonds with certain other nitrogenous bases in a complementary strand of nucleic acid. Adenine binds with thymine and uracil, thymine binds only with adenine, and cytosine and guanine can bind only with one another. Adenine, thymine, and uracil contain two hydrogen bonds, while hydrogen bonds formed between cytosine and guanine are three.

Aside from the genetic material of the cell, nucleic acids often play a role as second messengers, as well as forming the base molecule for adenosine triphosphate (ATP), the primary energy-carrier molecule found in all living organisms. Also, the nitrogenous bases possible in the two nucleic acids are different: adenine, cytosine, and guanine occur in both RNA and DNA, while thymine occurs only in DNA and uracil occurs in RNA.

Metabolism

[edit]

Carbohydrates as energy source

[edit]
Main articles: Carbohydrate metabolism and Carbon cycle

Glucose is an energy source in most life forms. For instance, polysaccharides are broken down into their monomers by enzymes (glycogen phosphorylase removes glucose residues from glycogen, a polysaccharide). Disaccharides like lactose or sucrose are cleaved into their two component monosaccharides.[49]

Glycolysis (anaerobic)

[edit]
A summary pathway diagram of glycolysis, showing the multi-step conversion of glucose to pyruvate. Each step in the pathway is catalysed by a unique enzyme.
The image above contains clickable links
The metabolic pathway of glycolysis converts glucose to pyruvate via a series of intermediate metabolites.    Each chemical modification is performed by a different enzyme.    Steps 1 and 3 consume ATP and    steps 7 and 10 produce ATP. Since steps 6–10 occur twice per glucose molecule, this leads to a net production of ATP.

Glucose is mainly metabolized by a very important ten-step pathway called glycolysis, the net result of which is to break down one molecule of glucose into two molecules of pyruvate. This also produces a net two molecules of ATP, the energy currency of cells, along with two reducing equivalents of converting NAD+ (nicotinamide adenine dinucleotide: oxidized form) to NADH (nicotinamide adenine dinucleotide: reduced form). This does not require oxygen; if no oxygen is available (or the cell cannot use oxygen), the NAD is restored by converting the pyruvate to lactate (lactic acid) (e.g. in humans) or to ethanol plus carbon dioxide (e.g. in yeast). Other monosaccharides like galactose and fructose can be converted into intermediates of the glycolytic pathway.[50]

Aerobic

[edit]

In aerobic cells with sufficient oxygen, as in most human cells, the pyruvate is further metabolized. It is irreversibly converted to acetyl-CoA, giving off one carbon atom as the waste product carbon dioxide, generating another reducing equivalent as NADH. The two molecules acetyl-CoA (from one molecule of glucose) then enter the citric acid cycle, producing two molecules of ATP, six more NADH molecules and two reduced (ubi)quinones (via FADH2 as enzyme-bound cofactor), and releasing the remaining carbon atoms as carbon dioxide. The produced NADH and quinol molecules then feed into the enzyme complexes of the respiratory chain, an electron transport system transferring the electrons ultimately to oxygen and conserving the released energy in the form of a proton gradient over a membrane (inner mitochondrial membrane in eukaryotes). Thus, oxygen is reduced to water and the original electron acceptors NAD+ and quinone are regenerated. This is why humans breathe in oxygen and breathe out carbon dioxide. The energy released from transferring the electrons from high-energy states in NADH and quinol is conserved first as proton gradient and converted to ATP via ATP synthase. This generates an additional 28 molecules of ATP (24 from the 8 NADH + 4 from the 2 quinols), totaling to 32 molecules of ATP conserved per degraded glucose (two from glycolysis + two from the citrate cycle).[51] It is clear that using oxygen to completely oxidize glucose provides an organism with far more energy than any oxygen-independent metabolic feature, and this is thought to be the reason why complex life appeared only after Earth's atmosphere accumulated large amounts of oxygen.

Gluconeogenesis

[edit]
Main article: Gluconeogenesis

In vertebrates, vigorously contracting skeletal muscles (during weightlifting or sprinting, for example) do not receive enough oxygen to meet the energy demand, and so they shift to anaerobic metabolism, converting glucose to lactate. The combination of glucose from noncarbohydrates origin, such as fat and proteins. This only happens when glycogen supplies in the liver are worn out. The pathway is a crucial reversal of glycolysis from pyruvate to glucose and can use many sources like amino acids, glycerol and Krebs Cycle. Large scale protein and fat catabolism usually occur when those suffer from starvation or certain endocrine disorders.[52] The liver regenerates the glucose, using a process called gluconeogenesis. This process is not quite the opposite of glycolysis, and actually requires three times the amount of energy gained from glycolysis (six molecules of ATP are used, compared to the two gained in glycolysis). Analogous to the above reactions, the glucose produced can then undergo glycolysis in tissues that need energy, be stored as glycogen (or starch in plants), or be converted to other monosaccharides or joined into di- or oligosaccharides. The combined pathways of glycolysis during exercise, lactate's crossing via the bloodstream to the liver, subsequent gluconeogenesis and release of glucose into the bloodstream is called the Cori cycle.[53]

Relationship to other "molecular-scale" biological sciences

[edit]
Schematic relationship between biochemistry, genetics, and molecular biology

Researchers in biochemistry use specific techniques native to biochemistry, but increasingly combine these with techniques and ideas developed in the fields of genetics, molecular biology, and biophysics. There is not a defined line between these disciplines. Biochemistry studies the chemistry required for biological activity of molecules, molecular biology studies their biological activity, genetics studies their heredity, which happens to be carried by their genome. This is shown in the following schematic that depicts one possible view of the relationships between the fields:

  • Biochemistry is the study of the chemical substances and vital processes occurring in live organisms. Biochemists focus heavily on the role, function, and structure of biomolecules. The study of the chemistry behind biological processes and the synthesis of biologically active molecules are applications of biochemistry. Biochemistry studies life at the atomic and molecular level.
  • Genetics is the study of the effect of genetic differences in organisms. This can often be inferred by the absence of a normal component (e.g. one gene). The study of "mutants" – organisms that lack one or more functional components with respect to the so-called "wild type" or normal phenotype. Genetic interactions (epistasis) can often confound simple interpretations of such "knockout" studies.
  • Molecular biology is the study of molecular underpinnings of the biological phenomena, focusing on molecular synthesis, modification, mechanisms and interactions. The central dogma of molecular biology, where genetic material is transcribed into RNA and then translated into protein, despite being oversimplified, still provides a good starting point for understanding the field. This concept has been revised in light of emerging novel roles for RNA.
  • Chemical biology seeks to develop new tools based on small molecules that allow minimal perturbation of biological systems while providing detailed information about their function. Further, chemical biology employs biological systems to create non-natural hybrids between biomolecules and synthetic devices (for example emptied viral capsids that can deliver gene therapy or drug molecules).

See also

[edit]
Main article: Outline of biochemistry

Lists

[edit]

See also

[edit]

Notes

[edit]

References

[edit]

Further reading

[edit]
[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Biochemistry

View on Grokipedia
from Grokipedia
Biochemistry is the branch of that studies the chemical substances and processes occurring in living organisms, integrating principles from and chemistry to understand life at the molecular level. It examines the structure, properties, and interactions of key biomolecules, including proteins, nucleic acids (such as and ), carbohydrates, and , which form the foundation of cellular function and organization. The field aims to explain biological phenomena through chemical mechanisms, revealing how these molecules enable processes like , , and genetic information transfer. The discipline of biochemistry emerged in the late 19th and early 20th centuries from chemical analyses of biological tissues, marking a shift from descriptive to molecular explanations of . Pioneering work, such as Eduard Buchner's 1897 demonstration of cell-free fermentation, established enzymes as catalysts for biochemical reactions, laying the groundwork for modern enzymology. By the early 1900s, advancements in isolating biological molecules and the advent of journals like Zeitschrift für Physiologische Chemie (founded 1877) solidified biochemistry as a distinct field, blending organic, inorganic, and physical chemistry with biology. This evolution accelerated in the mid-20th century with discoveries in molecular biology, including the structure of DNA in 1953, which illuminated the chemical basis of heredity. Biochemistry encompasses several core areas, including metabolism, which investigates how organisms convert food into energy and building blocks through interconnected pathways like and the ; enzymology, focusing on enzymes that accelerate reactions and are classified into six main categories such as oxidoreductases and hydrolases; and , exploring how nucleic acids store and transmit genetic information. Additional subfields include structural biochemistry, which analyzes biomolecular architectures using techniques like , and , which studies energy flow in cells. These areas highlight biochemistry's role in elucidating dynamic cellular processes, from protein synthesis to . The importance of biochemistry lies in its applications across diverse sectors, driving innovations in through targeting metabolic pathways and disease mechanisms, as well as in via that enhance nutrient efficiency. In health sciences, it informs by revealing how drugs interact with biomolecules, supports in assessing chemical toxicity, and advances through techniques like for development. Furthermore, biochemical insights into and improve dietary recommendations and , while contributions to address pollutant impacts on ecosystems. Overall, biochemistry provides the molecular framework for understanding and manipulating life processes, underpinning progress in human , , and .

History

Origins and Early Discoveries

The roots of biochemistry emerged from longstanding philosophical debates in the 18th and early 19th centuries between , which posited that living organisms were governed by a non-physical "vital force" distinct from ordinary chemical processes, and mechanism, which advocated that life could be explained through physical and chemical laws alone. This tension shaped early efforts to study biological phenomena chemically, as vitalists argued that organic compounds could only arise in , while mechanists sought to bridge the gap between inorganic and . A pivotal moment came in 1828 when German chemist synthesized —an found in —from inorganic , demonstrating that complex biological molecules could be produced in a without vital intervention. This experiment challenged vitalist doctrines by showing continuity between inorganic and organic realms, paving the way for viewing life as a series of chemical transformations, though its immediate impact on vitalism's decline was more symbolic than revolutionary. Building on such insights, French chemist conducted groundbreaking respiration experiments in the 1770s, measuring oxygen consumption and production in animals and humans, which framed breathing as a form of slow akin to chemical oxidation. These studies established as a quantifiable chemical process, linking physiological functions to elemental reactions and influencing later biochemical inquiries into energy transformation. In the 1840s, German chemist advanced these ideas through his work in physiological or "animal" chemistry, analyzing the chemical composition of foods and bodily fluids to elucidate metabolic pathways in and respiration. Liebig's experiments demonstrated that animal heat and work arose from the oxidation of and in foodstuffs, treating organisms as chemical engines and emphasizing the role of nitrogenous compounds in tissue repair. Toward the late , Emil Fischer's structural elucidations of sugars like glucose and proteins, including formations, provided foundational models for biomolecular architecture, revealing life's building blocks as intricate yet chemically analyzable entities. A culminating discovery occurred in 1897 when Eduard Buchner extracted a press-juice that fermented into alcohol and without intact cells, proving that enzymatic processes could operate extracorporeally and solidifying biochemistry's focus on isolated chemical mechanisms in . These milestones collectively shifted perceptions, portraying vital processes as governed by chemistry rather than mystical forces.

Development of Key Concepts and Techniques

The elucidation of the by Hans Krebs in 1937 marked a pivotal advancement in understanding , demonstrating how is oxidized through a series of enzymatic reactions involving intermediates to generate energy. Krebs' work, building on earlier observations of , integrated with and earned him the 1953 Nobel Prize in Physiology or Medicine, shared with Fritz Lipmann for discoveries on . This cycle became a cornerstone for subsequent research, highlighting the interconnectedness of biochemical processes. In the 1940s and 1950s, advanced protein by proposing the alpha-helix and beta-sheet configurations based on data and quantum mechanical principles, revolutionizing the understanding of polypeptide folding. Pauling's models emphasized hydrogen bonding's role in secondary structures, influencing later studies on protein function and earning recognition in his 1954 for chemical bond research. Concurrently, and Francis Crick's 1953 double-helix model of DNA provided a structural basis for genetic information storage and replication, integrating biochemical and crystallographic evidence from Rosalind Franklin's work. Their discovery, published in , laid the foundation for and was honored with the 1962 Nobel Prize in Physiology or Medicine, shared with . Technological innovations in the mid-20th century further propelled biochemical analysis. The development of in the 1950s, pioneered by for protein separation based on charge and size, enabled precise purification and characterization of biomolecules, earning Arne Tiselius the 1948 Nobel Prize in Chemistry for foundational electrophoretic methods. By the 1970s, (NMR) spectroscopy emerged as a non-destructive tool for determining molecular structures in solution, with Kurt Wüthrich's applications to proteins in the 1980s resolving three-dimensional folds and contributing to his 2002 . These techniques democratized structural biochemistry, allowing detailed studies of enzyme-substrate interactions and conformations. The 2010s introduced CRISPR-Cas9 as a transformative tool for biochemical manipulation, with and Emmanuelle Charpentier's 2012 demonstration of RNA-guided DNA cleavage enabling precise gene editing and studies. Their innovation, recognized with the 2020 shared with Charpentier, facilitated biochemical investigations into gene regulation and protein expression. Nobel recognitions underscored these shifts: the 1975 Chemistry Prize to for his studies on the of enzyme-catalyzed reactions, the 1980 Chemistry Prize to , , and for their contributions to the biochemistry of nucleic acids, including and sequencing, the 2023 or Medicine Prize to Katalin Karikó and for discoveries concerning base modifications that enabled the development of effective mRNA vaccines, and the 2024 Chemistry Prize to David Baker, , and John Jumper for computational and . Post-2000, biochemistry evolved toward integrative approaches like systems biochemistry, which models network-level interactions using computational tools to predict cellular responses. , advanced through high-throughput and NMR, profiles small-molecule metabolites to map dynamic pathways, as exemplified in global human projects initiated around 2007. A landmark in predictive modeling came with DeepMind's in 2020, achieving near-experimental accuracy in via AI, transforming structural and . These developments, incorporating genomic data, have unified biochemistry with , enabling holistic views of cellular function.

Chemical Foundations

Essential Elements and Atoms

Living organisms are primarily composed of a limited set of chemical elements, with six elements—oxygen (O), carbon (C), (H), (N), calcium (Ca), and (P)—accounting for approximately 99% of the mass in the . The elements carbon (C), (H), oxygen (O), (N), (P), and (S), collectively known as CHNOPS, form the foundational building blocks of biological molecules, enabling the complexity and functionality of life. Oxygen dominates by mass at approximately 65%, largely due to its prevalence in , which constitutes 60-70% of body weight, while carbon makes up about 18%, serving as the structural backbone for organic compounds. Hydrogen and follow at roughly 10% and 3%, respectively, contributing to , organic structures, and key biomolecules like proteins and nucleic acids. Calcium, at approximately 1.5%, is essential for mineralization and cellular signaling. Phosphorus and are present in smaller amounts, at about 1% and 0.25%, yet play critical roles in energy transfer molecules such as ATP and in like and . The roles of these elements are tightly linked to their chemical properties. Carbon's versatility stems from its ability to form four stable covalent bonds, arranged in a tetrahedral geometry that allows for diverse three-dimensional structures in biomolecules. This bonding capacity, combined with moderate (2.55 on the Pauling scale), enables carbon to create stable chains and rings essential for life's molecular diversity. ( 2.20) readily forms nonpolar bonds with carbon but polar bonds with more electronegative atoms like oxygen (3.44) and (3.04), facilitating hydrogen bonding crucial for molecular interactions. (2.19) and (2.58) contribute to high-energy bonds and disulfide bridges, respectively, due to their ability to form multiple oxidation states and polar linkages. Besides these major elements, trace elements constitute less than 1% of body mass but are indispensable for specific functions. For instance, iron (Fe), at under 0.01% of total mass, is central to , where it binds oxygen reversibly through changes between Fe²⁺ and Fe³⁺ states, enabling efficient transport in blood. Magnesium (Mg), comprising about 0.05%, forms the core of in , coordinating with nitrogenous ligands to absorb light for . These elements' low abundance belies their catalytic and structural importance, often as cofactors in enzymes. Isotopic variations of these elements also hold biological significance. (¹⁴C), a radioactive with a of 5,730 years, is incorporated into biomolecules during life via atmospheric CO₂ fixation and decays post-mortem, allowing to determine the age of organic remains up to about 50,000 years old. This technique has revolutionized biochemical studies of ancient ecosystems and molecular turnover rates, providing insights into evolutionary timelines without altering the primary elemental composition.
ElementApproximate % by Mass in Human BodyKey Biological Role
Oxygen (O)65Component of water and organic molecules; enables respiration
Carbon (C)18Backbone of organic structures
Hydrogen (H)10In water and C-H bonds for energy storage
Nitrogen (N)3In amino acids and nucleic acids
Calcium (Ca)1.5Structural component in bones and teeth; cellular signaling
Phosphorus (P)1In ATP, DNA, and phospholipids
Sulfur (S)0.25In cysteine, methionine, and coenzymes
Iron (Fe)<0.01Oxygen transport in hemoglobin
Magnesium (Mg)0.05Central ion in chlorophyll; enzyme cofactor

Role of Water and Acid-Base Chemistry

Water serves as the universal solvent in biological systems primarily due to its polarity, arising from the electronegative oxygen atom pulling electron density away from the hydrogen atoms, creating partial negative and positive charges, respectively. This polarity enables water molecules to form hydrogen bonds with each other and with polar solutes, such as ions and hydrophilic biomolecules, facilitating their dissolution and interactions essential for cellular processes. Hydrogen bonding also contributes to water's high specific heat capacity, approximately 4.18 J/g·°C, which allows it to absorb or release large amounts of heat with minimal temperature change, thereby stabilizing cellular temperatures during metabolic activities. In aqueous environments, water undergoes autoionization, where two water molecules react to produce hydronium (H₃O⁺) and hydroxide (OH⁻) ions, represented by the equilibrium equation: 2H2O⇌H3O++OH−\mathrm{2H_2O \rightleftharpoons H_3O^+ + OH^-} The equilibrium constant for this process, known as the ion product of water KwK_w, equals 1.0×10−141.0 \times 10^{-14} at 25°C, indicating that in pure water, the concentrations of H⁺ (or H₃O⁺) and OH⁻ are each 1.0×10−71.0 \times 10^{-7} M, resulting in a neutral pH of 7. Acid-base chemistry in biological systems is governed by the pH scale, defined as pH = −log₁₀[H⁺], which quantifies the hydrogen ion concentration and determines the acidity or basicity of solutions. Cellular processes require tight pH control, achieved through buffer systems that resist changes in pH upon addition of acids or bases. The Henderson-Hasselbalch equation describes the pH of such buffers: pH = pKₐ + log₁₀([A⁻]/[HA]), where pKₐ is the negative logarithm of the acid dissociation constant, [A⁻] is the conjugate base concentration, and [HA] is the acid concentration. In physiological contexts, the bicarbonate buffer system plays a critical role in maintaining blood pH around 7.4, with carbonic acid (H₂CO₃) having a pKₐ of 6.1, allowing it to effectively buffer against CO₂-derived acids from respiration. Intracellularly, the phosphate buffer system is prominent, particularly in the cytosol where the second dissociation of phosphoric acid (HPO₄²⁻/H₂PO₄⁻) has a pKₐ of 7.2, closely matching the typical cytosolic pH range of 7.2–7.4 and enabling stable conditions for enzymatic reactions and ion transport.

Biomolecules

Carbohydrates: Structure and Function

Carbohydrates are polyhydroxy aldehydes or ketones, or compounds that yield such units upon hydrolysis, consisting primarily of carbon, hydrogen, and oxygen in a 1:2:1 ratio. They serve as essential biomolecules in living organisms, functioning as rapid energy sources through oxidation and as structural components in cell walls and exoskeletons. Classified by polymerization degree, carbohydrates include monosaccharides (single units), disaccharides (two units), and polysaccharides (many units linked by glycosidic bonds). Their structures determine solubility, digestibility, and biological roles, with variations in linkage types (α or β) influencing helical or linear conformations. Monosaccharides are the building blocks of carbohydrates, simple sugars with 3 to 7 carbon atoms and the general formula \ce(CH2O)n\ce{(CH2O)_n}, where n typically ranges from 3 to 7. , an aldohexose with molecular formula \ceC6H12O6\ce{C6H12O6}, exemplifies this class and is ubiquitous in biology. In its open-chain form, glucose is depicted in a Fischer projection as a straight chain with an aldehyde group at C1, hydroxyl groups on C2–C5 (configuring as D-glucose with the C5 OH on the right), and a CH2OH at C6. However, in aqueous solution, over 99% of glucose exists in cyclic forms via intramolecular hemiacetal formation, where the C5 hydroxyl attacks the C1 carbonyl, predominantly yielding a six-membered pyranose ring (β-D-glucopyranose or α-D-glucopyranose, differing at the anomeric C1). This cyclization introduces a new chiral center at C1, enabling α (axial OH) and β (equatorial OH) anomers, which interconvert via mutarotation. Disaccharides form when two monosaccharides join via a glycosidic bond, an acetal linkage from dehydration of hemiacetal and hydroxyl groups, releasing water. Sucrose, a non-reducing disaccharide, comprises α-D-glucose and β-D-fructose connected by an α-1,2-glycosidic bond, making it the primary transport sugar in plants and a key dietary source. Lactose, a reducing disaccharide in mammalian milk, links β-D-galactose to D-glucose through a β-1,4-glycosidic bond, providing energy for infants and serving as a precursor for other galactosides. These linkages dictate enzymatic digestibility; for instance, lactase hydrolyzes the β-1,4 bond in lactose. Polysaccharides are long chains of monosaccharides (often hundreds to thousands of units) polymerized via glycosidic bonds, enabling diverse functions based on linkage stereochemistry. , the plant energy storage polysaccharide, includes (linear α-1,4-linked D-glucose, forming a left-handed helix) and (branched with α-1,6 linkages every 24–30 residues), allowing compact storage and rapid mobilization. , the analogous animal storage form in liver and muscle, is more branched (α-1,6 every 8–12 residues) than amylopectin, facilitating quicker glucose release during energy demands. In contrast, provides structural support in plant cell walls as linear β-1,4-linked D-glucose chains, which hydrogen-bond into rigid microfibrils resistant to hydrolysis. , a nitrogen-containing structural polysaccharide, consists of β-1,4-linked N-acetyl-D-glucosamine units, forming tough fibers in arthropod exoskeletons and fungal cell walls. Carbohydrates fulfill critical biological functions as energy providers, stores, and structural elements. Glucose oxidation via cellular respiration yields approximately 30 ATP molecules per molecule, underscoring its role as a universal fuel. Storage polysaccharides like glycogen and starch maintain glucose homeostasis, with glycogenolysis releasing glucose-1-phosphate for metabolic use. Structurally, cellulose imparts tensile strength to plants, enabling upright growth, while chitin reinforces invertebrate cuticles against mechanical stress. Glycoconjugates extend carbohydrate functionality by covalently attaching oligosaccharides to proteins or lipids, forming glycoproteins that mediate cell adhesion, signaling, and immune recognition. In N-linked glycosylation, oligosaccharides attach to asparagine residues in Asn-X-Ser/Thr motifs via an N-acetylglucosamine intermediate, occurring co-translationally in the endoplasmic reticulum. O-linked glycosylation, attaching to serine or threonine hydroxyls, proceeds in the Golgi via direct galactosamine or other sugar transfer, contributing to mucin-like protections and protein stability. These modifications influence glycoprotein folding, trafficking, and interactions with lectins.

Lipids: Structure and Function

Lipids are a diverse class of hydrophobic biomolecules primarily composed of carbon, hydrogen, and oxygen, essential for cellular structure, energy storage, and signaling in living organisms. Unlike other biomolecules, lipids are defined more by their solubility in nonpolar solvents than by a single structural motif, encompassing simple lipids like fatty acids and complex ones like phospholipids and steroids. Their amphipathic properties—possessing both hydrophilic and hydrophobic regions—enable critical roles in forming barriers and facilitating molecular interactions. Fatty acids serve as the foundational building blocks of most lipids, consisting of a hydrocarbon chain attached to a carboxylic acid group. They are classified as saturated if the chain lacks double bonds, such as palmitic acid (C16:0), a 16-carbon straight-chain molecule common in animal fats, or unsaturated if containing one or more double bonds, like oleic acid (C18:1). Saturated fatty acids typically have even-numbered carbon chains ranging from 14 to 24 atoms, contributing to the rigidity of lipid structures. Unsaturated variants introduce kinks that affect packing and fluidity. Triglycerides, or triacylglycerols, are formed by esterifying three fatty acid molecules to a glycerol backbone, creating neutral, nonpolar storage lipids. These molecules aggregate into droplets in adipose tissue, serving as the primary energy reserve in animals and plants due to their high caloric density—approximately 9 kcal per gram. For instance, in human adipocytes, triglycerides composed of saturated and monounsaturated fatty acids like palmitic and oleic acid predominate, enabling efficient long-term energy storage. Phospholipids are key amphipathic lipids that constitute the bulk of cell membranes, featuring a glycerol spine linked to two hydrophobic fatty acid tails, a phosphate group, and a polar head, as in phosphatidylcholine (glycerol + two fatty acids + phosphate + choline). This structure allows phospholipids to self-assemble into bilayers, with hydrophilic heads facing aqueous environments and hydrophobic tails sequestered inward, forming a semipermeable barrier that regulates cellular transport and maintains compartmentalization. The diversity in fatty acid chain length (C14–C26) and saturation further modulates bilayer properties, such as thickness and permeability. Steroids, including cholesterol, possess a characteristic four-fused-ring system (three six-membered and one five-membered) with a hydroxyl group at one end and a flexible hydrocarbon tail, rendering them rigid and planar. Cholesterol, abundant in eukaryotic membranes, intercalates between phospholipid tails to modulate fluidity—preventing excessive rigidity at low temperatures and excessive disorder at high ones—thus maintaining optimal membrane integrity. Sphingolipids, another membrane component, feature a sphingoid base (e.g., sphingosine) backbone amide-linked to a fatty acid, forming ceramides that can attach polar heads like phosphocholine in sphingomyelin. These lipids cluster in ordered membrane domains, contributing to signaling platforms and cellular recognition. In terms of function, lipids excel in energy provision through β-oxidation of fatty acids, where each cycle cleaves two carbons as acetyl-CoA, yielding 4 ATP equivalents per round via NADH and FADH₂ oxidation in the electron transport chain. For example, complete β-oxidation of palmitic acid (C16:0) generates 8 acetyl-CoA units and nets approximately 106 ATP molecules, far exceeding glucose oxidation yields per carbon atom and underscoring lipids' role in sustained energy during fasting. Membrane lipids like phospholipids and cholesterol ensure structural stability and fluidity, integrating briefly with proteins to form functional complexes such as lipid rafts. Additionally, lipids act as precursors for signaling molecules; arachidonic acid (C20:4 n-6), an unsaturated fatty acid, is released from membrane phospholipids to produce eicosanoids like prostaglandins, which mediate inflammation and homeostasis. Steroids from cholesterol further serve as hormone precursors, such as cortisol and sex hormones, regulating diverse physiological processes.

Proteins: Structure and Function

Proteins are linear polymers composed of amino acid monomers linked by peptide bonds, serving as the primary functional units in cellular processes due to their diverse structures and roles. The 20 standard amino acids found in proteins share a common backbone structure consisting of a central α-carbon atom bonded to a hydrogen atom, a carboxyl group (-COOH), an amino group (-NH₂), and a variable side chain (R group). In aqueous environments at physiological pH, amino acids predominantly exist as zwitterions, where the carboxyl group is deprotonated to -COO⁻ and the amino group is protonated to -NH₃⁺, resulting in a net neutral charge but with separated positive and negative charges. The properties of the R group determine the amino acid's classification: nonpolar (hydrophobic) side chains, such as those in alanine (methyl group) and leucine (isobutyl group), promote interactions in non-aqueous environments; polar uncharged side chains, like those in serine (hydroxymethyl) and asparagine (amide), enable hydrogen bonding; and charged side chains include acidic ones, such as aspartic acid (carboxymethyl, negatively charged at pH 7) and basic ones, such as lysine (butylamine, positively charged at pH 7). The primary structure of a protein is its linear sequence of amino acids, dictated by the genetic code from messenger RNA and determining all higher levels of organization. Secondary structure arises from local hydrogen bonding between the backbone atoms, forming regular motifs such as the α-helix, proposed by and Robert Corey in 1951, where the polypeptide chain coils into a right-handed spiral stabilized by hydrogen bonds between the carbonyl oxygen of one residue and the amide hydrogen four residues ahead, and the β-sheet, also described by and Corey, consisting of extended strands aligned either parallel or antiparallel with hydrogen bonds between adjacent strands. Tertiary structure represents the overall three-dimensional fold of a single polypeptide chain, driven by interactions among side chains and the backbone, including a hydrophobic core where nonpolar residues cluster away from water to minimize free energy, as demonstrated in studies of protein folding, and covalent disulfide bonds formed between the thiol groups of cysteine residues to stabilize the fold, particularly in extracellular proteins. Quaternary structure occurs in proteins composed of multiple polypeptide subunits, assembled through noncovalent interactions and sometimes disulfide bonds; for example, human consists of two α and two β subunits arranged in a tetrahedral configuration, enabling cooperative oxygen binding. Proteins exhibit a wide array of functions shaped by their structures. As enzymes, they catalyze biochemical reactions by providing an active site that lowers activation energy through precise substrate binding and orientation, exemplified by ribonuclease A, whose folding was shown to be thermodynamically driven by Anfinsen's experiments in the 1960s. In transport roles, proteins such as hemoglobin facilitate the movement of oxygen across membranes via its heme-binding pockets, while ion channels like the potassium channel form selective pores lined by polar residues to allow passive diffusion. Defense functions are fulfilled by antibodies, which are Y-shaped immunoglobulins with variable regions that bind specific antigens through complementary shapes, triggering immune responses. Structural proteins provide mechanical support; collagen, the most abundant protein in animals, forms a triple helix from three left-handed polyproline II-like chains wound into a right-handed superhelix, rich in glycine, proline, and hydroxyproline, imparting tensile strength to connective tissues. Post-translational modifications expand protein diversity and functionality beyond the primary sequence encoded by nucleic acids. Phosphorylation involves the addition of a phosphate group to serine, threonine, or tyrosine residues by kinases, introducing negative charge that can alter protein conformation, activity, or interactions, as seen in signal transduction pathways. Ubiquitination attaches , a small 76-amino-acid protein, to lysine residues via a cascade of E1, E2, and E3 enzymes, often marking proteins for proteasomal degradation but also regulating non-degradative processes like trafficking.

Nucleic Acids: Structure and Function

Nucleic acids are essential biomolecules that serve as the primary carriers of genetic information in living organisms, composed of repeating nucleotide units. Each nucleotide consists of a nitrogenous base attached to a five-carbon sugar (pentose) and at least one phosphate group, with nucleotides linked by phosphodiester bonds between the sugar of one nucleotide and the phosphate of the next, forming a directional sugar-phosphate backbone. The nitrogenous bases fall into two classes: purines (adenine [A] and guanine [G]) and pyrimidines (cytosine [C], thymine [T] in DNA, or uracil [U] in RNA). In deoxyribonucleic acid (DNA), the sugar is 2'-deoxyribose, lacking a hydroxyl group at the 2' carbon position, whereas ribonucleic acid (RNA) contains ribose with a hydroxyl group at that site. The structure of DNA is a right-handed double helix, in which two antiparallel polynucleotide strands wind around a common axis, stabilized by hydrogen bonding between complementary bases: A pairs with T via two hydrogen bonds, and G pairs with C via three. This Watson-Crick base pairing ensures specificity in genetic information storage and dictates the sequence of one strand based on the other. The most prevalent conformation in vivo is the B-form, characterized by approximately 10.5 base pairs per helical turn, a pitch (axial rise per turn) of 3.4 nm, a diameter of about 2 nm, and nearly perpendicular base pairs to the helix axis, resulting in major and minor grooves that facilitate protein interactions. These grooves expose the edges of the bases, allowing regulatory proteins to bind and access the genetic code without unwinding the helix. In contrast, RNA is generally single-stranded, enabling it to fold into complex secondary and tertiary structures through intramolecular base pairing, which influences its diverse roles. The three major types of RNA include messenger RNA (mRNA), which is linear and conveys genetic instructions from DNA; transfer RNA (tRNA), which adopts a characteristic cloverleaf secondary structure with stem-loops, including an anticodon loop for base-pairing with mRNA; and ribosomal RNA (rRNA), which forms intricate folded structures as a core component of ribosomes. These RNA structures enable specific functions, such as tRNA's role in recognizing codons during protein assembly. Nucleic acids primarily function in the storage, transmission, and expression of hereditary information. DNA maintains genetic continuity through semiconservative replication, in which each parental strand serves as a template for a new complementary strand, producing two identical daughter molecules. This mechanism, demonstrated experimentally using density-labeled DNA in Escherichia coli, ensures faithful copying of the genome across cell divisions. In gene expression, DNA is transcribed into RNA transcripts, which are then translated into proteins, with RNA serving as an intermediary to direct the synthesis of functional polypeptides from the genetic blueprint.

Enzymes and Catalysis

Enzyme Structure and Mechanism

Enzymes are primarily proteins, though some RNA molecules also exhibit catalytic activity, that accelerate biochemical reactions by lowering activation energies through specific structural features. The core of an enzyme's catalytic function resides in its active site, a specialized region typically formed by a pocket or cleft on the protein surface where substrates bind and undergo transformation. This site is composed of amino acid residues precisely positioned to interact with the substrate, often involving hydrogen bonds, electrostatic interactions, and van der Waals forces to achieve specificity. The classical model for substrate binding, proposed by Emil Fischer in 1894, describes the active site as a rigid, preformed structure complementary in shape, charge, and hydrophobic properties to the substrate, analogous to a lock and key fitting precisely to ensure specificity. This lock-and-key hypothesis explained the high selectivity of enzymes like glycosidases for particular sugar configurations but failed to account for cases where substrates induce structural adjustments in the enzyme. In 1958, Daniel Koshland introduced the induced fit model, positing that substrate binding triggers conformational changes in the enzyme, reshaping the active site for optimal alignment and catalysis, thereby enhancing specificity and efficiency beyond mere geometric complementarity. This dynamic process is exemplified in , where glucose binding causes a large hinge motion that closes the active site, excluding water and positioning catalytic residues. Amino acid residues in the active site, such as those in , play critical roles; for instance, the catalytic triad consisting of aspartate (Asp), histidine (His), and serine (Ser) residues facilitates nucleophilic attack on peptide bonds. In , Asp102 orients His57 for proton abstraction from Ser195, enabling the serine hydroxyl to act as a nucleophile in forming a covalent acyl-enzyme intermediate. Enzyme mechanisms often involve acid-base catalysis, where residues donate or accept protons to stabilize transition states. In ribonuclease A, His12 and His119 act as general bases and acids, respectively, to facilitate the hydrolysis of RNA phosphodiester bonds via a 2'-3'-cyclic phosphate intermediate. Another common strategy employs covalent intermediates, as seen in ping-pong mechanisms where the enzyme alternates between substrates. Nucleoside diphosphate kinase (NDPK), for example, uses a phosphohistidine intermediate: the enzyme first transfers phosphate from ATP to His122, forming a phosphoenzyme, then transfers it to GDP, enabling sequential phosphoryl group exchange. Many enzymes require cofactors to achieve full catalytic competence, as their protein scaffolds alone lack necessary chemical groups. Metal ions like Zn^{2+} serve as Lewis acids, polarizing substrates or stabilizing charged intermediates; in carbonic anhydrase, Zn^{2+} coordinated to three histidine residues deprotonates a bound water molecule, generating a Zn^{2+}-OH^- nucleophile that attacks CO_2 to form bicarbonate (HCO_3^-). Zn2+−OH−+CO2→Zn2+−OCO2−+H+\text{Zn}^{2+}-\text{OH}^- + \text{CO}_2 \rightarrow \text{Zn}^{2+}-\text{OCO}_2^- + \text{H}^+ This reaction proceeds at near-diffusion-limited rates, underscoring the ion's role in enhancing nucleophilicity. Coenzymes, organic cofactors derived from vitamins, participate directly in catalysis; nicotinamide adenine dinucleotide (NAD^+), composed of nicotinamide and adenine nucleotides linked by a pyrophosphate bond, accepts a hydride ion (H^-) from substrates in dehydrogenation reactions. For example, NAD^+-dependent enzymes, such as alcohol dehydrogenase, oxidize alcohols to aldehydes or ketones, thereby reducing NAD^+ to NADH. \ceR−CH2OH+NAD+⇌R−CHO+NADH+H+\ce{R-CH2OH + NAD^+ ⇌ R-CHO + NADH + H^+} The nicotinamide ring's C4 position stereospecifically accepts the pro-R hydride, ensuring reaction specificity. Beyond the active site, allosteric sites—distinct binding pockets—allow regulatory molecules to induce conformational changes that modulate catalysis, a phenomenon first formalized by Monod, Wyman, and Changeux in 1965. Effector binding at these sites shifts the enzyme between tense (T, low-activity) and relaxed (R, high-activity) states, as in hemoglobin's cooperative oxygen binding, but applied to enzymes like aspartate transcarbamoylase where CTP binding stabilizes the T state to inhibit activity. Such changes propagate through the protein via altered hydrogen bonding networks or rigid-body motions, fine-tuning substrate affinity without directly competing at the active site.00391-7)

Enzyme Kinetics and Regulation

Enzyme kinetics quantifies the rates of enzymatic reactions and how they depend on substrate concentration, providing a framework for understanding catalytic efficiency. The foundational model is the Michaelis-Menten equation, which assumes a simple reversible binding of substrate to enzyme followed by product formation, yielding the initial reaction velocity vv as v=Vmax⁡[S]Km+[S]v = \frac{V_{\max} [S]}{K_m + [S]}, where Vmax⁡V_{\max} is the maximum velocity achieved at saturating substrate concentration [S][S], and KmK_m is the Michaelis constant representing the substrate concentration at which v=12Vmax⁡v = \frac{1}{2} V_{\max}. This equation, derived from steady-state assumptions, highlights hyperbolic saturation kinetics typical of many enzymes and enables determination of kinetic parameters through nonlinear regression or linear transformations. A common linearization, the Lineweaver-Burk plot, transforms the Michaelis-Menten equation into 1v=KmVmax⁡⋅1[S]+1Vmax⁡\frac{1}{v} = \frac{K_m}{V_{\max}} \cdot \frac{1}{[S]} + \frac{1}{V_{\max}}, plotting 1v\frac{1}{v} versus 1[S]\frac{1}{[S]} to yield a straight line with slope KmVmax⁡\frac{K_m}{V_{\max}}, y-intercept 1Vmax⁡\frac{1}{V_{\max}}, and x-intercept −1Km-\frac{1}{K_m}. This graphical method facilitates parameter estimation and analysis of deviations, such as those caused by inhibitors, though it can amplify errors at low substrate concentrations. Enzyme inhibition modulates kinetics by reducing activity, classified by effects on KmK_m and Vmax⁡V_{\max} in Lineweaver-Burk plots. Competitive inhibition occurs when an inhibitor binds reversibly to the active site, competing with substrate and increasing apparent KmK_m (reduced substrate affinity) while Vmax⁡V_{\max} remains unchanged, as higher [S][S] can outcompete the inhibitor; the modified equation is v=Vmax⁡[S]Km(1+[I]Ki)+[S]v = \frac{V_{\max} [S]}{K_m (1 + \frac{[I]}{K_i}) + [S]}, where [I][I] is inhibitor concentration and KiK_i is the inhibition constant. Noncompetitive inhibition involves binding to a site distinct from the active site, unaffected by substrate presence, decreasing Vmax⁡V_{\max} (fewer functional enzymes) but leaving KmK_m unchanged, with the equation v=Vmax⁡[S](Km+[S])(1+[I]Ki)v = \frac{V_{\max} [S]}{(K_m + [S])(1 + \frac{[I]}{K_i})}. Uncompetitive inhibition binds only to the enzyme-substrate complex, lowering both KmK_m (apparent increased affinity) and Vmax⁡V_{\max}, yielding parallel lines in Lineweaver-Burk plots, described by v=Vmax⁡[S]Km+[S](1+[I]Ki)v = \frac{V_{\max} [S]}{K_m + [S](1 + \frac{[I]}{K_i})}. Beyond inhibition, enzymes are regulated physiologically to fine-tune metabolic flux. Allosteric regulation involves effector binding at sites remote from the active site, inducing conformational changes that alter activity; for instance, feedback inhibition in aspartate transcarbamoylase (ATCase), a key enzyme in pyrimidine biosynthesis, is allosterically inhibited by (CTP), the pathway's end product, reducing activity to prevent overproduction, while (ATP) acts as an activator.65038-6/fulltext) This heterotropic regulation exemplifies the Monod-Wyman-Changeux concerted model, where effectors shift equilibrium between tense (low-affinity) and relaxed (high-affinity) states. Covalent modification provides rapid, reversible control, often via phosphorylation that adds a negatively charged phosphate group to serine, threonine, or tyrosine residues, altering charge and conformation. A classic example is glycogen phosphorylase, where phosphorylation by phosphorylase kinase converts the inactive b form to the active a form, enhancing glycogen breakdown in response to hormonal signals like epinephrine.74379-8/fulltext) Zymogens represent irreversible activation through proteolytic cleavage, ensuring enzymes like proteases remain inactive until needed; trypsinogen, secreted by the pancreas, is converted to active trypsin by enterokinase in the intestine, cleaving a peptide bond to expose the active site and initiate protein digestion. Environmental factors also influence kinetics: temperature affects rate via Arrhenius kinetics, with most enzymes exhibiting optimal activity around 37°C in humans before denaturation reduces Vmax⁡V_{\max}, while extremes inactivate via unfolding. pH optima, typically near neutrality for cytoplasmic enzymes (e.g., pH 7 for ), arise from protonation states of active-site residues; deviations alter KmK_m and Vmax⁡V_{\max} by ionizing key groups, as seen in 's acidic optimum (pH 2) for gastric function.

Metabolism

Catabolic Pathways

Catabolic pathways in biochemistry encompass the degradative processes that break down complex biomolecules, such as carbohydrates, lipids, and proteins, into simpler molecules, thereby releasing energy in the form of ATP and reducing equivalents like NADH and FADH₂. These pathways converge on central routes, including glycolysis, the tricarboxylic acid (TCA) cycle, β-oxidation, and amino acid degradation, which funnel substrates into energy-yielding reactions while producing CO₂ as a byproduct. Primarily occurring in the cytosol and mitochondria, these processes provide substrates for oxidative phosphorylation, enabling cells to meet energetic demands under varying conditions. Glycolysis, also known as the Embden-Meyerhof-Parnas pathway, is a universal 10-step anaerobic process that converts one molecule of glucose into two molecules of pyruvate, occurring in the cytosol of nearly all cells. The pathway begins with the phosphorylation of glucose by or , consuming ATP, followed by isomerization to fructose-6-phosphate and another ATP-dependent phosphorylation to fructose-1,6-bisphosphate. Cleavage by aldolase yields dihydroxyacetone phosphate and , which interconvert via triose phosphate isomerase; the latter then undergoes oxidation by to 1,3-bisphosphoglycerate, producing NADH. Subsequent steps involve substrate-level phosphorylation to generate ATP via and , resulting in a net yield of 2 ATP, 2 NADH, and 2 pyruvate per glucose molecule. The overall reaction is: glucose+2ADP+2Pi+2NAD+→2pyruvate+2ATP+2NADH+2H++2H2O\text{glucose} + 2 \text{ADP} + 2 \text{P}_\text{i} + 2 \text{NAD}^+ \rightarrow 2 \text{pyruvate} + 2 \text{ATP} + 2 \text{NADH} + 2 \text{H}^+ + 2 \text{H}_2\text{O} Under aerobic conditions, pyruvate enters the mitochondria for further oxidation, linking glycolysis to the TCA cycle. The TCA cycle, or Krebs cycle, serves as the central hub for oxidizing acetyl-CoA derived from carbohydrates, fats, and proteins, completing the catabolism of pyruvate from glycolysis and other sources. This eight-step cyclic pathway occurs in the mitochondrial matrix and begins with the condensation of acetyl-CoA (two carbons) with oxaloacetate (four carbons) by citrate synthase to form citrate, followed by isomerization to isocitrate. Oxidative decarboxylation by isocitrate dehydrogenase produces α-ketoglutarate, NADH, and CO₂; α-ketoglutarate dehydrogenase then yields succinyl-CoA, another NADH, and CO₂. Succinyl-CoA synthetase generates GTP (or ATP) and succinate, which is dehydrogenated to fumarate by succinate dehydrogenase, producing FADH₂. Fumarase hydrates fumarate to malate, and malate dehydrogenase oxidizes it back to oxaloacetate, yielding a third NADH. Per acetyl-CoA, the cycle produces 3 NADH, 1 FADH₂, 1 GTP, and 2 CO₂, with no net accumulation of intermediates due to the regenerative nature of the cycle. β-Oxidation is the primary catabolic route for fatty acids, sequentially cleaving two-carbon units as acetyl-CoA from the carboxyl end of activated acyl-CoA chains in the mitochondrial matrix. The process initiates with activation of free fatty acids to acyl-CoA by acyl-CoA synthetase in the cytosol or outer mitochondrial membrane, requiring ATP and producing AMP and pyrophosphate; the acyl group is then transported into the matrix via the carnitine shuttle. Each cycle of β-oxidation comprises four enzymatic steps: dehydrogenation by acyl-CoA dehydrogenase to form a trans-enoyl-CoA and FADH₂; hydration by enoyl-CoA hydratase to L-3-hydroxyacyl-CoA; oxidation by 3-hydroxyacyl-CoA dehydrogenase to 3-ketoacyl-CoA and NADH; and thiolysis by β-ketothiolase to acetyl-CoA and a shortened acyl-CoA. For a saturated even-chain fatty acid like palmitate (16 carbons), seven cycles yield eight acetyl-CoA, 7 FADH₂, and 7 NADH, which feed into the TCA cycle and electron transport chain for maximal energy extraction. Amino acid catabolism involves the initial removal of the α-amino group through transamination, transferring it to α-ketoglutarate to form glutamate and the corresponding α-keto acid, primarily catalyzed by aminotransferases like alanine aminotransferase or aspartate aminotransferase. These α-keto acids, such as pyruvate from alanine or oxaloacetate from aspartate, then enter central catabolic pathways: glucogenic amino acids feed into gluconeogenesis or the TCA cycle at points like α-ketoglutarate, succinyl-CoA, or fumarate, while ketogenic ones like leucine produce acetyl-CoA or acetoacetate for the TCA cycle or ketogenesis. The ammonia from deamination is detoxified via the urea cycle, ensuring nitrogen homeostasis during protein breakdown. This integration allows amino acids to contribute to energy production, with yields varying by residue but ultimately converging on the TCA cycle for oxidation.

Anabolic Pathways

Anabolic pathways in biochemistry encompass the energy-requiring processes that synthesize complex biomolecules from simpler precursors, essential for growth, repair, and maintenance of cellular structures. These pathways contrast with by building macromolecules such as carbohydrates, lipids, nucleotides, and amino acids, often drawing on intermediates from central metabolism like the tricarboxylic acid (TCA) cycle. In anabolic reactions, ATP and reducing equivalents like NADPH drive the formation of carbon-carbon bonds and other linkages, ensuring the production of molecules critical for cellular function. Gluconeogenesis represents a primary anabolic route for carbohydrate synthesis, generating glucose from non-carbohydrate precursors such as lactate, glycerol, and amino acids, primarily in the liver and kidneys to maintain blood glucose levels during fasting. This pathway largely reverses glycolysis but circumvents its three irreversible steps—those catalyzed by , phosphofructokinase-1, and pyruvate kinase—through specialized enzymes. The conversion of pyruvate to oxaloacetate is mediated by pyruvate carboxylase, a biotin-dependent enzyme that requires ATP and occurs in the mitochondria, while phosphoenolpyruvate carboxykinase (PEPCK) then decarboxylates oxaloacetate to phosphoenolpyruvate using GTP, predominantly in the cytosol. Additional bypasses include fructose-1,6-bisphosphatase and glucose-6-phosphatase, which hydrolyze their respective phosphate esters without energy input. Overall, synthesizing one glucose molecule from two pyruvates demands six high-energy phosphate bonds (four ATP and two GTP equivalents), highlighting the energetic cost of this reversal. Fatty acid synthesis constructs long-chain fatty acids from acetyl-CoA units, occurring in the cytosol and serving as a key step in lipid anabolism for membrane formation and energy storage. The process initiates with the carboxylation of acetyl-CoA to malonyl-CoA by acetyl-CoA carboxylase, an ATP-dependent reaction that provides the two-carbon donor for chain elongation while preventing futile cycling with β-oxidation. Malonyl-CoA is then transferred to the fatty acid synthase (FAS) complex, a multifunctional enzyme that iteratively adds two-carbon units from malonyl-CoA to the growing acyl chain, releasing CO₂ in each condensation step. Each elongation cycle involves β-ketoacyl reduction, dehydration, and enoyl reduction, all powered by NADPH as the electron donor, ultimately yielding palmitate (C16:0) after seven cycles. This NADPH dependence underscores the pathway's reliance on reductive biosynthesis, with the FAS complex coordinating all activities in a single polypeptide in mammals.01125-X) Nucleotide synthesis occurs via de novo and salvage pathways, enabling the production of purine and pyrimidine nucleotides for DNA, RNA, and cofactor assembly. In de novo purine biosynthesis, the pathway assembles the purine ring stepwise on 5-phosphoribosyl-1-pyrophosphate (PRPP), starting with the activation of PRPP by glutamine phosphoribosyl pyrophosphate amidotransferase to form 5-phosphoribosylamine, followed by additions of glycine, formate, aspartate, and CO₂ to yield inosine monophosphate (IMP). Pyrimidine de novo synthesis first constructs the ring as orotate from carbamoyl phosphate and aspartate, then attaches it to PRPP via orotate phosphoribosyltransferase to form orotidine monophosphate, which is decarboxylated to uridine monophosphate (UMP). These pathways require ATP for multiple steps and integrate one-carbon units from folate metabolism. Salvage pathways, in contrast, recycle free bases or nucleosides—such as adenine via adenine phosphoribosyltransferase with PRPP to AMP, or hypoxanthine to IMP—conserving energy and precursors from nucleic acid turnover. Amino acid biosynthesis draws heavily from TCA cycle intermediates as carbon skeletons, allowing cells to produce non-essential amino acids from central metabolic pools. For instance, glutamate is synthesized by the reductive amination of α-ketoglutarate using glutamate dehydrogenase, which transfers an amino group from ammonia (or glutamine via glutamate synthase) in an NADPH-dependent reaction, serving as a precursor for glutamine, proline, and arginine. Aspartate derives from oxaloacetate through transamination with glutamate, feeding into asparagine, lysine, methionine, threonine, and isoleucine synthesis. Other TCA-derived amino acids include alanine from pyruvate (a glycolysis-TCA link) and the branched-chain group from α-ketoglutarate and oxaloacetate branches. These pathways are amphibolic, linking anabolism to TCA flux and nitrogen assimilation, with glutamate acting as a key nitrogen donor across multiple routes.

Metabolic Integration and Regulation

Metabolic pathways in eukaryotic cells are organized into distinct subcellular compartments, which facilitates efficient integration and prevents futile cycles between catabolism and anabolism. Glycolysis, the initial breakdown of glucose to pyruvate, occurs primarily in the cytosol, allowing rapid response to energy demands without the need for organelle transport. In contrast, the tricarboxylic acid (TCA) cycle takes place in the mitochondrial matrix, where it links carbohydrate, lipid, and protein catabolism to oxidative phosphorylation for ATP production. Beta-oxidation of fatty acids is compartmentalized between peroxisomes, which handle the initial shortening of very-long-chain fatty acids, and mitochondria for complete oxidation, ensuring specialized handling of hydrophobic substrates. This spatial separation is maintained by membrane transporters, such as the mitochondrial pyruvate carrier, which shuttles metabolites between cytosol and mitochondria to coordinate flux across pathways. Hormonal signals further integrate metabolic pathways by modulating enzyme activities in response to systemic energy needs, promoting homeostasis through reciprocal actions on anabolism and catabolism. Insulin, secreted in response to elevated blood glucose, promotes anabolic processes by activating glycogen synthase through dephosphorylation via the IRS-PI3K-Akt pathway, thereby enhancing glucose storage as glycogen in liver and muscle. This action inhibits gluconeogenesis and lipolysis while stimulating glycolysis and lipogenesis, directing nutrients toward storage. Conversely, glucagon, released during low glucose states, drives catabolic pathways by elevating cyclic AMP levels via G-protein-coupled receptors, which activates protein kinase A to promote hepatic glycogenolysis and gluconeogenesis, increasing blood glucose availability. Glucagon also stimulates fatty acid oxidation and amino acid catabolism, counteracting insulin's effects to mobilize energy reserves during fasting or stress. At the cellular level, reciprocal regulation ensures that catabolic and anabolic pathways do not operate simultaneously, with key enzymes like phosphofructokinase-1 (PFK-1) serving as control points for glycolytic flux. PFK-1 is allosterically inhibited by high ATP and citrate, signals of energy abundance and active TCA cycle, respectively, which prevents unnecessary glucose breakdown when cellular needs are met. In energy-deficient states, PFK-1 is activated by AMP, indicating low ATP levels, and by fructose-2,6-bisphosphate, a potent regulator produced by PFK-2 that overrides ATP inhibition to favor glycolysis over gluconeogenesis. This feed-forward and feedback mechanism integrates cytosolic glycolysis with mitochondrial oxidation, allowing cells to adjust flux dynamically to maintain redox and energy balance. Metabolic flux analysis provides a quantitative framework for understanding how perturbations in one pathway affect overall integration, emphasizing distributed control rather than single rate-limiting steps. Flux control coefficients, introduced by Kacser and Burns, measure the fractional change in steady-state flux through a pathway in response to a fractional change in enzyme activity, revealing that control is often shared among multiple steps. For instance, in glycolysis, enzymes like hexokinase and PFK-1 may have higher coefficients under varying conditions, guiding how hormonal or compartmental signals redistribute flux for homeostasis. This approach highlights the robustness of integrated networks, where compensatory adjustments in enzyme levels or activities maintain steady-state metabolism despite external changes.

Bioenergetics

Thermodynamic Principles

In biochemistry, the Gibbs free energy change, denoted as ΔG, serves as a fundamental criterion for determining the spontaneity of chemical reactions under constant temperature and pressure. It is defined by the equation ΔG=ΔH−TΔS\Delta G = \Delta H - T \Delta S where ΔH represents the change in enthalpy, T is the absolute temperature in Kelvin, and ΔS is the change in entropy. This relationship integrates the energetic (enthalpic) and disorder-related (entropic) contributions to a process, allowing biochemists to predict whether a reaction will proceed without external energy input. For standard conditions, particularly in aqueous solutions at pH 7 (denoted as ΔG°'), the standard Gibbs free energy change relates to the equilibrium constant K_eq via ΔG∘=−RTln⁡Keq\Delta G^\circ = -RT \ln K_\text{eq} where R is the gas constant (8.314 J/mol·K). A reaction is spontaneous if ΔG < 0, indicating that the products are more stable than the reactants and the process favors forward progression toward equilibrium. Biochemical reactions are classified as exergonic (ΔG < 0, energy-releasing and spontaneous) or endergonic (ΔG > 0, energy-requiring and non-spontaneous). In living systems, endergonic processes essential for biosynthesis or transport are rarely isolated; instead, they are coupled to exergonic reactions to achieve an overall negative ΔG. A classic example is the hydrolysis of adenosine triphosphate (ATP) to adenosine diphosphate (ADP) and inorganic phosphate (Pi), with ΔG°' ≈ -30.5 kJ/mol under standard biochemical conditions (pH 7); the actual ΔG under physiological conditions is more negative, approximately -50 kJ/mol, which drives unfavorable syntheses such as the formation of glutamine from glutamate and ammonia. This coupling mechanism underscores ATP's role as a universal energy currency in cells, enabling the thermodynamic feasibility of otherwise improbable reactions. Many biological reactions operate far from equilibrium, characterized by equilibrium constants K_eq that are either extremely large (>>1) or small (<<1), corresponding to large negative or positive ΔG° values, respectively. These near-irreversible reactions (large negative ΔG°) ensure directional flux in metabolic pathways, preventing wasteful back-reactions and maintaining cellular . profoundly influences biochemical processes through its effect on ΔG, as the TΔS term amplifies entropic contributions at higher temperatures. Reaction rates in biology often exhibit a Q_{10} effect, where rates approximately double (Q_{10} ≈ 2) for every 10°C increase, reflecting the Arrhenius temperature dependence integrated into thermodynamic feasibility. This sensitivity ensures that physiological temperatures optimize both spontaneity and kinetics in enzymatic .

Energy Carriers and Redox Processes

(ATP) serves as the primary energy carrier in cellular processes, consisting of an base linked to a sugar and three groups attached via phosphoanhydride bonds. The high-energy phosphoanhydride bonds between the groups store significant potential energy due to electrostatic repulsion among the negatively charged phosphates, making thermodynamically favorable with a standard free energy change of ΔG°' ≈ -30.5 kJ/mol. This hydrolysis reaction cleaves the terminal phosphoanhydride bond, yielding (ADP) and inorganic (Pi), thereby releasing energy to drive endergonic reactions in . In redox processes, coenzymes such as (NAD⁺/NADH) and (FAD/FADH₂) act as electron carriers, facilitating between metabolic pathways. The of these carriers determines their ability to donate or accept electrons, quantified by the : E=E∘′+RTnFln⁡([ox][red])E = E^{\circ'} + \frac{RT}{nF} \ln \left( \frac{[\text{ox}]}{[\text{red}]} \right) where EE is the actual reduction potential, E∘′E^{\circ'} is the standard reduction potential at 7, RR is the , TT is in , nn is the number of electrons transferred, FF is the , and [ox][\text{ox}] and [red][\text{red}] are the concentrations of the oxidized and reduced forms, respectively. For NAD⁺/NADH, the standard reduction potential E∘′E^{\circ'} is -0.32 V, indicating a strong , while for free FAD/FADH₂ it is approximately -0.22 V, though this value varies when bound to enzymes. These potentials enable NADH and FADH₂ to donate electrons to the (ETC), powering . The electron transport chain comprises four membrane-bound protein complexes (I–IV) embedded in the inner mitochondrial membrane, which sequentially accept electrons from NADH and FADH₂ to generate a proton gradient. Complex I (NADH dehydrogenase) oxidizes NADH and transfers electrons to ubiquinone while pumping protons (H⁺) across the membrane; Complex II (succinate dehydrogenase) handles FADH₂-derived electrons without proton pumping; Complex III (cytochrome bc₁) passes electrons to cytochrome c and pumps additional protons; and Complex IV (cytochrome c oxidase) reduces oxygen to water, further contributing to the proton gradient. This vectorial proton translocation establishes an electrochemical gradient (proton-motive force) across the membrane, with approximately 10 H⁺ translocated per NADH oxidized. The chemiosmotic theory, proposed by Peter Mitchell in 1961, posits that this proton gradient directly drives ATP synthesis without requiring high-energy chemical intermediates. , a rotary complex consisting of the membrane-embedded F₀ subunit (proton channel) and the peripheral F₁ subunit (catalytic head), harnesses the proton-motive force as protons flow back into the matrix, inducing conformational changes that phosphorylate ADP to ATP. This mechanism integrates redox-driven proton pumping with efficient energy conservation, underpinning aerobic respiration.

Interdisciplinary Connections

Biochemistry intersects with molecular biology through the chemical processes that govern the flow of genetic information, as encapsulated in the central dogma proposed by Francis Crick, which states that genetic information flows from DNA to RNA to proteins, with no reverse transfer from proteins to nucleic acids. This unidirectional pathway relies on biochemical reactions involving nucleotide polymerization and hydrolysis, ensuring the fidelity and efficiency of information transfer in cells. In prokaryotes and eukaryotes, these processes are catalyzed by enzymes that utilize energy from nucleotide triphosphates, highlighting biochemistry's role in enabling molecular biology's core mechanisms. Transcription, the synthesis of RNA from a DNA template, begins when binds to promoter sequences, such as the in eukaryotes, approximately 25-30 upstream of the transcription start site. In eukaryotes, , responsible for mRNA synthesis, forms a pre-initiation complex with general transcription factors like TFIID, which recognizes the promoter and recruits the polymerase, initiating RNA chain elongation through formation. This biochemical mechanism ensures precise , with the promoter's core elements dictating the start site and regulatory sequences modulating the rate. Translation converts the of mRNA into a polypeptide chain at ribosomes, which are ribonucleoprotein complexes that decode the via the codon table, where each three- codon specifies an or stop signal. The process involves transfer RNAs (tRNAs) carrying to the ribosome's A site, where peptidyl transferase activity—catalyzed by —forms peptide bonds, driven by GTP hydrolysis for translocation. This biochemical orchestration achieves high efficiency, with ribosomes synthesizing proteins at rates up to 20 per second in bacteria, underscoring the interplay between chemistry and . DNA replication maintains genetic integrity by duplicating the genome semi-conservatively, with DNA polymerases adding nucleotides to the 3' end of a growing strand in a 5' to 3' direction, using deoxynucleoside triphosphates as substrates. On the lagging strand, discontinuous synthesis produces Okazaki fragments, short RNA-primed DNA segments (typically 100-200 nucleotides in eukaryotes) that are later joined by DNA ligase after primer removal. Proofreading fidelity is enhanced by the polymerase's 3' to 5' exonuclease activity, which excises mismatched nucleotides, reducing error rates to about 1 in 10^7 base pairs incorporated. Gene regulation at the molecular level integrates biochemical signals to control expression, as exemplified by the in , where the protein, encoded by the lacI gene, binds the operator sequence to block transcription in the absence of , but binding induces a conformational change, releasing the and allowing access. Enhancers, distal DNA elements often thousands of base pairs from promoters, boost transcription by looping to interact with promoter-bound factors, recruiting co-activators like to enhance activity. Epigenetic modifications, such as at CpG islands by DNA methyltransferases, add methyl groups to residues, recruiting repressive proteins like methyl-CpG-binding domain proteins that compact and inhibit binding, thereby silencing genes biochemically without altering the sequence. RNA processing in eukaryotes matures pre-mRNA through splicing, where the —a complex of snRNPs—recognizes intron-exon boundaries and catalyzes two reactions to excise introns and ligate exons, ensuring accurate coding sequence assembly. Capping occurs co-transcriptionally at the 5' end, adding a 7-methylguanosine cap via guanylyltransferase and methyltransferases, which protects against exonucleases and facilitates binding during . Polyadenylation at the 3' end involves cleavage at a poly(A) signal (AAUAAA) followed by addition of 200-250 residues by , stabilizing the mRNA, promoting nuclear export, and enhancing translational efficiency through cap-tail synergy. Biochemistry intersects with through advanced techniques that elucidate the three-dimensional architectures of biomolecules, essential for understanding their functions. X-ray crystallography remains a cornerstone method, providing atomic-resolution structures of proteins and complexes, though it is constrained by resolution limits typically around 1-3 due to crystal quality and radiation damage. A key challenge in this technique is the phase problem, where diffraction experiments yield only amplitude information, requiring methods like multiple isomorphous replacement or molecular replacement to determine phases and reconstruct maps. Complementing crystallography, (cryo-EM) has revolutionized the field by enabling high-resolution imaging of large macromolecular assemblies without crystallization, such as the bacterial at 1.55 resolution, revealing dynamic conformational states inaccessible to other methods. Biophysical principles underpin these structural insights by governing molecular interactions at the atomic level. Van der Waals forces, arising from transient interactions, contribute to the stability of close-packed atomic surfaces in protein interfaces and ligand binding. Electrostatic interactions, including salt bridges and hydrogen bonds between charged residues, play a critical role in protein-DNA binding, facilitating sequence-specific recognition in transcription factors like the . of biomolecules, vital for cellular processes, follows Fick's first law, where the JJ is given by J=−D∇CJ = -D \nabla C with DD as the and ∇C\nabla C the concentration gradient, influencing reaction rates in crowded cellular environments. Protein folding exemplifies the integration of structural and biophysical perspectives, where the Levinthal paradox highlights the improbability of random conformational searches reaching the native state within biological timescales, necessitating guided pathways. Molecular chaperones like Hsp70 assist by binding hydrophobic regions of nascent or misfolded polypeptides, preventing aggregation and promoting refolding through ATP-dependent cycles. Misfolding can lead to pathogenic aggregates, such as amyloid-β fibrils in Alzheimer's disease, which disrupt cellular proteostasis and contribute to neurodegeneration. In membrane biophysics, lipid rafts—cholesterol- and sphingolipid-enriched domains—organize channels and receptors, modulating their localization and activity in . gating, the conformational switch between open and closed states, is influenced by tension and composition, enabling selective permeation crucial for neuronal signaling and . These principles reveal how physical forces dictate biochemical function, with techniques like cryo-EM capturing transient gating intermediates.

References

  1. https://www.acs.org/careers/chemical-sciences/areas/biochemistry.html
  2. https://www.mtu.edu/chemistry/undergraduate/biochemistry/what/
  3. https://libguides.library.nd.edu/biochemistry
  4. https://www.vassar.edu/biochemistry/history
  5. https://www.ncbi.nlm.nih.gov/books/NBK554481/
  6. https://pmc.ncbi.nlm.nih.gov/articles/PMC7217401/
  7. https://mechanism.ucsd.edu/bill/teaching/philbio/vitalism.htm
  8. https://pmc.ncbi.nlm.nih.gov/articles/PMC6208063/
  9. https://pubmed.ncbi.nlm.nih.gov/2003841/
  10. https://www.researchgate.net/publication/236977897_Antoine-Laurent_de_Lavoisier_1743-1794_and_the_birth_of_respiratory_physiology
  11. https://www.researchgate.net/publication/9087501_Justus_Liebig_and_Animal_Chemistry
  12. https://www.uni-giessen.de/en/about/portrait/historyjlu/eponym
  13. https://www.nobelprize.org/prizes/chemistry/1902/fischer/biographical/
  14. https://mechanism.ucsd.edu/~bill/teaching/w22/phil147/buchner.1897.pdf
  15. https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.200700390
  16. https://www.nobelprize.org/prizes/chemistry/1975/cornforth/facts/
  17. https://www.nobelprize.org/prizes/chemistry/1980/summary/
  18. https://www.nobelprize.org/prizes/chemistry/2024/summary/
  19. https://www.ncbi.nlm.nih.gov/books/NBK26883/
  20. https://bio.libretexts.org/Bookshelves/Introductory_and_General_Biology/General_Biology_1e_%28OpenStax%29/1%253A_The_Chemistry_of_Life/2%253A_The_Chemical_Foundation_of_Life/2.3%253A_Carbon
  21. https://bioprinciples.biosci.gatech.edu/biological-molecules-2/
  22. https://www.thoughtco.com/elemental-composition-human-body-by-mass-608192
  23. https://pmc.ncbi.nlm.nih.gov/articles/PMC3999603/
  24. https://pmc.ncbi.nlm.nih.gov/articles/PMC9085447/
  25. https://www.acs.org/education/whatischemistry/landmarks/radiocarbon-dating.html
  26. https://chem.libretexts.org/Bookshelves/Physical_and_Theoretical_Chemistry_Textbook_Maps/Supplemental_Modules_%28Physical_and_Theoretical_Chemistry%29/Nuclear_Chemistry/Applications_of_Nuclear_Chemistry/Radiocarbon_Dating
  27. https://biology.arizona.edu/biochemistry/tutorials/chemistry/page3.html
  28. https://pmc.ncbi.nlm.nih.gov/articles/PMC5639468/
  29. https://open.maricopa.edu/hazards/chapter/14-1-unique-properties-of-water/
  30. https://chem.libretexts.org/Bookshelves/General_Chemistry/Map%3A_Chemistry_-_The_Central_Science_(Brown_et_al.)/16%3A_AcidBase_Equilibria/16.03%3A_The_Autoionization_of_Water
  31. https://courses.lumenlearning.com/suny-dutchess-introbio2/chapter/ph-acids-bases-and-buffers/
  32. https://globalrph.com/medcalcs/henderson-hasselbalch-equation/
  33. https://www.sciencedirect.com/topics/medicine-and-dentistry/henderson-hasselbalch-equation
  34. https://chemistry.ucsd.edu/undergraduate/student-resources/CHEM40-Chapter09-UCSD-ED-23-24.pdf
  35. https://www.sciencedirect.com/science/article/pii/S1386142520313895
  36. https://www.ncbi.nlm.nih.gov/books/NBK459280/
  37. https://www.ncbi.nlm.nih.gov/books/NBK579984/
  38. https://content.byui.edu/file/a236934c-3c60-4fe9-90aa-d343b3e3a640/1/module3/readings/carbohydrates.html
  39. https://employees.csbsju.edu/hjakubowski/classes/ch125/ib4_imf_carbohydrates.html
  40. https://www.ncbi.nlm.nih.gov/books/NBK579981/
  41. https://www.chem.fsu.edu/~rlight/4053s01/Lectures/Chapter07.pdf
  42. https://web.pdx.edu/~wamserc/C336S02/25notes.htm
  43. https://pressbooks-dev.oer.hawaii.edu/biology/chapter/carbohydrates/
  44. https://opened.cuny.edu/courseware/lesson/613/student/?section=2
  45. https://books.byui.edu/bio_264_anatomy_phy_I/disaccharides
  46. https://wou.edu/chemistry/chapter-11-introduction-major-macromolecules/
  47. https://opened.cuny.edu/courseware/lesson/613/overview
  48. https://bio.libretexts.org/Bookshelves/Microbiology/Microbiology_(Kaiser)/Unit_7:_Microbial_Genetics_and_Microbial_Metabolism/18:_Microbial_Metabolism/18.3:_Aerobic_Respiration/18.3E:_Theoretical_ATP_Yield
  49. https://rockedu.rockefeller.edu/component/carbohydrate-background/
  50. https://pmc.ncbi.nlm.nih.gov/articles/PMC8618160/
  51. https://www.ncbi.nlm.nih.gov/books/NBK525952/
  52. https://pmc.ncbi.nlm.nih.gov/articles/PMC3995129/
  53. https://pmc.ncbi.nlm.nih.gov/articles/PMC8578989/
  54. https://www.ncbi.nlm.nih.gov/books/NBK556002/
  55. https://www.ncbi.nlm.nih.gov/books/NBK555990/
  56. https://chemed.chem.purdue.edu/genchem/topicreview/bp/1biochem/amino2.html
  57. https://www.ncbi.nlm.nih.gov/books/NBK557845/
  58. https://www.ncbi.nlm.nih.gov/books/NBK564343/
  59. https://www.pnas.org/doi/10.1073/pnas.2034522100
  60. https://www.ncbi.nlm.nih.gov/books/NBK470269/
  61. https://pmc.ncbi.nlm.nih.gov/articles/PMC7370311/
  62. https://pmc.ncbi.nlm.nih.gov/articles/PMC2846778/
  63. https://www.ncbi.nlm.nih.gov/books/NBK28487/
  64. https://www.ncbi.nlm.nih.gov/books/NBK26821/
  65. https://www.nature.com/articles/171737a0
  66. https://www.ncbi.nlm.nih.gov/books/NBK26887/
  67. https://www.ncbi.nlm.nih.gov/books/NBK558999/
  68. https://www.pnas.org/doi/10.1073/pnas.44.7.671
  69. https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lock-key-model
  70. https://www.medschool.lsuhsc.edu/biochemistry/docs/Lichtenthaler.pdf
  71. https://onlinelibrary.wiley.com/doi/abs/10.1002/anie.199423751
  72. https://www.sciencedirect.com/science/article/pii/S0021925820540635
  73. https://pubs.acs.org/doi/abs/10.1021/ja00038a067
  74. https://wou.edu/chemistry/courses/online-chemistry-textbooks/ch450-and-ch451-biochemistry-defining-life-at-the-molecular-level/chapter-7-catalytic-mechanisms-of-enzymes/
  75. https://febs.onlinelibrary.wiley.com/doi/10.1046/j.1432-1327.2001.02070.x
  76. https://pubs.acs.org/doi/10.1021/ar9501232
  77. https://pmc.ncbi.nlm.nih.gov/articles/PMC7486293/
  78. https://chem.libretexts.org/Bookshelves/Biological_Chemistry/Supplemental_Modules_%28Biological_Chemistry%29/Vitamins_Cofactors_and_Coenzymes/Nicotinamide_Adenine_Dinucleotide_%28NAD%29
  79. https://www.nature.com/articles/s41392-020-00311-7
  80. https://pmc.ncbi.nlm.nih.gov/articles/PMC3381512/
  81. https://pubs.acs.org/doi/10.1021/ja01318a036
  82. https://pubmed.ncbi.nlm.nih.gov/3030738/
  83. https://chem.libretexts.org/Bookshelves/General_Chemistry/Book%253A_Structure_and_Reactivity_in_Organic_Biological_and_Inorganic_Chemistry_%28Schaller%29/III%253A_Reactivity_in_Organic_Biological_and_Inorganic_Chemistry_1/07%253A_Metabolic_Pathways/7.01%253A_An_Overview_of_Metabolic_Pathways_-_Catabolism
  84. https://www.ncbi.nlm.nih.gov/books/NBK556032/
  85. https://portlandpress.com/essaysbiochem/article/64/4/607/226177/Metabolism
  86. https://www.ncbi.nlm.nih.gov/books/NBK482303/
  87. https://www.nature.com/articles/s41392-023-01569-3
  88. https://pmc.ncbi.nlm.nih.gov/articles/PMC10421169/
  89. https://www.ncbi.nlm.nih.gov/books/NBK541119/
  90. https://www.annualreviews.org/doi/pdf/10.1146/annurev-nutr-061121-091507
  91. https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/gluconeogenesis
  92. https://pmc.ncbi.nlm.nih.gov/articles/PMC4276719/
  93. https://www.sciencedirect.com/topics/immunology-and-microbiology/fatty-acid-synthesis
  94. https://pmc.ncbi.nlm.nih.gov/articles/PMC3243375/
  95. https://pmc.ncbi.nlm.nih.gov/articles/PMC8015690/
  96. https://pmc.ncbi.nlm.nih.gov/articles/PMC4703346/
  97. https://pmc.ncbi.nlm.nih.gov/articles/PMC10155461/
  98. https://pmc.ncbi.nlm.nih.gov/articles/PMC6515536/
  99. https://pubmed.ncbi.nlm.nih.gov/9075792/
  100. https://pmc.ncbi.nlm.nih.gov/articles/PMC10980016/
  101. https://www.nature.com/articles/s41467-024-51808-6
  102. https://pubmed.ncbi.nlm.nih.gov/2598934/
  103. http://guweb2.gonzaga.edu/faculty/cronk/CHEM245pub/free_energy.html
  104. https://bioprinciples.biosci.gatech.edu/04-energy-and-enzymes/
  105. https://ocw.mit.edu/courses/5-07sc-biological-chemistry-i-fall-2013/74228ba954337f8b27fc2c894c988a5d_MIT5_07SCF13_Lec10.pdf
  106. https://ocw.mit.edu/courses/7-012-introduction-to-biology-fall-2004/98fdd5975f947254273eb1d7cd1000c3_lecture5notes.pdf
  107. https://ocw.mit.edu/courses/7-014-introductory-biology-spring-2005/09508eb4025eac92d7a3e954e3ec46f5_l5_bioche_deltag.pdf
  108. https://www.physiologyweb.com/calculators/q10_calculator.html
  109. https://www.ncbi.nlm.nih.gov/books/NBK553175/
  110. https://open.lib.umn.edu/humanbiology/chapter/4-5-atp-adenosine-triphosphate/
  111. https://book.bionumbers.org/what-is-the-redox-potential-of-a-cell/
  112. https://sceweb.sce.uhcl.edu/wang/biochem/redox/4_reduction_potential.html
  113. https://www.ncbi.nlm.nih.gov/books/NBK526105/
  114. https://www.nobelprize.org/uploads/2018/06/mitchell-lecture.pdf
  115. https://www.nature.com/articles/227561a0
  116. https://www.ncbi.nlm.nih.gov/books/NBK9935/
  117. https://www.ncbi.nlm.nih.gov/books/NBK26829/
  118. https://pmc.ncbi.nlm.nih.gov/articles/PMC6153641/
  119. https://pmc.ncbi.nlm.nih.gov/articles/PMC5377794/
  120. https://pubmed.ncbi.nlm.nih.gov/13718526/
  121. https://pmc.ncbi.nlm.nih.gov/articles/PMC4445073/
  122. https://www.nature.com/articles/npp2012112
  123. https://www.sciencedirect.com/science/article/pii/S0092867402006177
  124. https://pmc.ncbi.nlm.nih.gov/articles/PMC7614307/
  125. https://pmc.ncbi.nlm.nih.gov/articles/PMC1186895/
  126. https://people.bu.edu/mfk/restricted566/phaseproblem.pdf
  127. https://www.nature.com/articles/s41467-023-36742-3
  128. https://williams.chemistry.gatech.edu/structure/molecular_interactions/mol_int.html
  129. https://pubs.acs.org/doi/10.1021/acs.accounts.0c00212
  130. https://bookdown.org/jcog196013/BS1005/mechanisms-of-protein-folding.html
  131. https://pmc.ncbi.nlm.nih.gov/articles/PMC2982175/
  132. https://pmc.ncbi.nlm.nih.gov/articles/PMC5573152/
  133. https://pmc.ncbi.nlm.nih.gov/articles/PMC2976012/
Add your contribution
Related Hubs
User Avatar
No comments yet.