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Fatty acid synthesis
In biochemistry, fatty acid synthesis is the creation of fatty acids from acetyl-CoA and NADPH through the action of enzymes. Two de novo fatty acid syntheses can be distinguished: cytosolic fatty acid synthesis (FAS/FASI) and mitochondrial fatty acid synthesis (mtFAS/mtFASII). Most of the acetyl-CoA which is converted into fatty acids is derived from carbohydrates via the glycolytic pathway. The glycolytic pathway also provides the glycerol with which three fatty acids can combine (by means of ester bonds) to form triglycerides (also known as "triacylglycerols" – to distinguish them from fatty "acids" – or simply as "fat"), the final product of the lipogenic process. When only two fatty acids combine with glycerol and the third alcohol group is phosphorylated with a group such as phosphatidylcholine, a phospholipid is formed. Phospholipids form the bulk of the lipid bilayers that make up cell membranes and surrounds the organelles within the cells (such as the cell nucleus, mitochondria, endoplasmic reticulum, Golgi apparatus, etc.).
Straight-chain fatty acids occur in two types: saturated and unsaturated. The latter are produced from the former.
Straight-chain fatty acid synthesis occurs via the six recurring reactions shown below, until the 16-carbon palmitic acid is produced.
The diagrams presented show how fatty acids are synthesized in microorganisms and list the enzymes found in Escherichia coli. These reactions are performed by fatty acid synthase II (FASII), which in general contain multiple enzymes that act as one complex. FASII is present in prokaryotes, plants, fungi, and parasites, and also in the mitochondria of animals, including humans.
In animals, as well as some fungi such as yeast, de novo fatty acid synthesis in the cytosol is carried out by fatty acid synthase I (FASI), a large dimeric protein that has all of the enzymatic activities required to create a fatty acid. FASII is less efficient than FASI; however, it allows for the formation of more molecules, including "medium-chain" fatty acids via early chain termination. The mitochondrial FASII system (also referred to as mtFAS) plays essential roles in mitochondrial function, such as lipoic acid biosynthesis and regulation of respiratory chain activity.
Once formed by FASI, the 16:0 carbon fatty acid can undergo a number of modifications, resulting in desaturation and/or elongation. Elongation to stearate (18:0) mainly occurs in the ER by several membrane-bound enzymes. The steps involved in the elongation process are principally the same as those carried out by FAS, but the four principal successive steps of the elongation are performed by individual proteins, which may be physically associated.
In fatty synthesis, the reducing agent is NADPH, whereas NAD is the oxidizing agent in beta-oxidation (the breakdown of fatty acids to acetyl-CoA). This difference exemplifies a general principle that NADPH is consumed during biosynthetic reactions, whereas NADH is generated in energy-yielding reactions. (Thus NADPH is also required for the synthesis of cholesterol from acetyl-CoA; while NADH is generated during glycolysis.) The source of the NADPH is two-fold. When malate is oxidatively decarboxylated by "NADP+-linked malic enzyme" to form pyruvate, CO2 and NADPH are formed. NADPH is also formed by the pentose phosphate pathway which converts glucose into ribose, which can be used in synthesis of nucleotides and nucleic acids, or it can be catabolized to pyruvate.
In humans, fatty acids are formed from carbohydrates predominantly in the liver and adipose tissue, as well as in the mammary glands during lactation.
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Fatty acid synthesis
In biochemistry, fatty acid synthesis is the creation of fatty acids from acetyl-CoA and NADPH through the action of enzymes. Two de novo fatty acid syntheses can be distinguished: cytosolic fatty acid synthesis (FAS/FASI) and mitochondrial fatty acid synthesis (mtFAS/mtFASII). Most of the acetyl-CoA which is converted into fatty acids is derived from carbohydrates via the glycolytic pathway. The glycolytic pathway also provides the glycerol with which three fatty acids can combine (by means of ester bonds) to form triglycerides (also known as "triacylglycerols" – to distinguish them from fatty "acids" – or simply as "fat"), the final product of the lipogenic process. When only two fatty acids combine with glycerol and the third alcohol group is phosphorylated with a group such as phosphatidylcholine, a phospholipid is formed. Phospholipids form the bulk of the lipid bilayers that make up cell membranes and surrounds the organelles within the cells (such as the cell nucleus, mitochondria, endoplasmic reticulum, Golgi apparatus, etc.).
Straight-chain fatty acids occur in two types: saturated and unsaturated. The latter are produced from the former.
Straight-chain fatty acid synthesis occurs via the six recurring reactions shown below, until the 16-carbon palmitic acid is produced.
The diagrams presented show how fatty acids are synthesized in microorganisms and list the enzymes found in Escherichia coli. These reactions are performed by fatty acid synthase II (FASII), which in general contain multiple enzymes that act as one complex. FASII is present in prokaryotes, plants, fungi, and parasites, and also in the mitochondria of animals, including humans.
In animals, as well as some fungi such as yeast, de novo fatty acid synthesis in the cytosol is carried out by fatty acid synthase I (FASI), a large dimeric protein that has all of the enzymatic activities required to create a fatty acid. FASII is less efficient than FASI; however, it allows for the formation of more molecules, including "medium-chain" fatty acids via early chain termination. The mitochondrial FASII system (also referred to as mtFAS) plays essential roles in mitochondrial function, such as lipoic acid biosynthesis and regulation of respiratory chain activity.
Once formed by FASI, the 16:0 carbon fatty acid can undergo a number of modifications, resulting in desaturation and/or elongation. Elongation to stearate (18:0) mainly occurs in the ER by several membrane-bound enzymes. The steps involved in the elongation process are principally the same as those carried out by FAS, but the four principal successive steps of the elongation are performed by individual proteins, which may be physically associated.
In fatty synthesis, the reducing agent is NADPH, whereas NAD is the oxidizing agent in beta-oxidation (the breakdown of fatty acids to acetyl-CoA). This difference exemplifies a general principle that NADPH is consumed during biosynthetic reactions, whereas NADH is generated in energy-yielding reactions. (Thus NADPH is also required for the synthesis of cholesterol from acetyl-CoA; while NADH is generated during glycolysis.) The source of the NADPH is two-fold. When malate is oxidatively decarboxylated by "NADP+-linked malic enzyme" to form pyruvate, CO2 and NADPH are formed. NADPH is also formed by the pentose phosphate pathway which converts glucose into ribose, which can be used in synthesis of nucleotides and nucleic acids, or it can be catabolized to pyruvate.
In humans, fatty acids are formed from carbohydrates predominantly in the liver and adipose tissue, as well as in the mammary glands during lactation.