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Tyrosine
Skeletal formula of the L-isomer
Skeletal formula of the L-isomer
Skeletal formula of L-tyrosine
L-Tyrosine at physiological pH
Names
IUPAC name
Tyrosine
Systematic IUPAC name
2-Amino-3-(4-hydroxyphenyl)propanoic acid
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.000.419 Edit this at Wikidata
KEGG
UNII
  • InChI=1S/C9H11NO3/c10-8(9(12)13)5-6-1-3-7(11)4-2-6/h1-4,8,11H,5,10H2,(H,12,13)/t8-/m0/s1 checkY
    Key: OUYCCCASQSFEME-QMMMGPOBSA-N checkY
  • Key: OUYCCCASQSFEME-UHFFFAOYSA-N
  • Key: OUYCCCASQSFEME-MRVPVSSYSA-N
  • N[C@@H](Cc1ccc(O)cc1)C(O)=O
  • Zwitterion: [NH3+][C@@H](Cc1ccc(O)cc1)C([O-])=O
Properties
C9H11NO3
Molar mass 181.191 g·mol−1
Appearance white solid
45.3 mg/100 mL
−105.3·10−6 cm3/mol
Hazards
NFPA 704 (fire diamond)
NFPA 704 four-colored diamondHealth 1: Exposure would cause irritation but only minor residual injury. E.g. turpentineFlammability 1: Must be pre-heated before ignition can occur. Flash point over 93 °C (200 °F). E.g. canola oilInstability 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no code
1
1
0
Supplementary data page
Tyrosine (data page)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Tyrosine ball and stick model spinning

L-Tyrosine or tyrosine (symbol Tyr or Y)[2] or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a conditionally essential amino acid with a polar side group. The word "tyrosine" is from the Greek tyrós, meaning cheese, as it was first discovered in 1846 by German chemist Justus von Liebig in the protein casein from cheese.[3][4] It is called tyrosyl when referred to as a functional group or side chain. While tyrosine is generally classified as a hydrophobic amino acid, it is more hydrophilic than phenylalanine.[5] It is encoded by the codons UAC and UAU in messenger RNA.

The one-letter symbol Y was assigned to tyrosine for being alphabetically nearest of those letters available. Note that T was assigned to the structurally simpler threonine, U was avoided for its similarity with V for valine, W was assigned to tryptophan, while X was reserved for undetermined or atypical amino acids.[6] The mnemonic tYrosine was also proposed.[7]

Functions

[edit]

Aside from being a proteinogenic amino acid, tyrosine has a special role by virtue of the phenol functionality. Its hydroxy group is able to form the ester linkage, with phosphate in particular. Phosphate groups are transferred to tyrosine residues by way of protein kinases. This is one of the post-translational modifications. Phosphorylated tyrosine occurs in proteins that are part of signal transduction processes.

Similar functionality is also presented in serine and threonine, whose side chains have a hydroxy group, but are alcohols. Phosphorylation of these three amino acids' moieties (including tyrosine) creates a negative charge on their ends, which is greater than the negative charge of the only negatively charged aspartic and glutamic acids. Phosphorylated proteins keep these same properties—which are useful for more reliable protein-protein interactions—by means of phosphotyrosine, phosphoserine and phosphothreonine.[8]

Binding sites for a signalling phosphoprotein may be diverse in their chemical structure.[9]

Phosphorylation of the hydroxyl group can change the activity of the target protein, or may form part of a signaling cascade via SH2 domain binding.[10]

A tyrosine residue also plays an important role in photosynthesis. In chloroplasts (photosystem II), it acts as an electron donor in the reduction of oxidized chlorophyll. In this process, it loses the hydrogen atom of its phenolic OH-group. This radical is subsequently reduced in the photosystem II by the four core manganese clusters.[11]

Dietary requirements and sources

[edit]

The Dietary Reference Intake for tyrosine is usually estimated together with phenylalanine. It varies depending on an estimate method, however the ideal proportion of these two amino acids is considered to be 60:40 (phenylalanine:tyrosine) as a human body has such composition.[12] Tyrosine, which can also be synthesized in the body from phenylalanine, is found in many high-protein food products such as meat, fish, cheese, cottage cheese, milk, yogurt, peanuts, almonds, pumpkin seeds, sesame seeds, soy protein and lima beans.[13][14] For example, the white of an egg has about 250 mg per egg,[15] while beef, lamb, pork, tuna, salmon, chicken, and turkey contain about 500–1000 mg per 3 ounces (85 g) portion.[15][16]

Biosynthesis

[edit]
Plant biosynthesis of tyrosine from prephenate.

In plants and most microorganisms, tyrosine is produced via prephenate, an intermediate on the shikimate pathway. Prephenate is oxidatively decarboxylated with retention of the hydroxyl group to give p-hydroxyphenylpyruvate, which is transaminated using glutamate as the nitrogen source to give tyrosine and α-ketoglutarate.

Mammals synthesize tyrosine from the essential amino acid phenylalanine (Phe), which is derived from food. The conversion of Phe to Tyr is catalyzed by the enzyme phenylalanine hydroxylase, a monooxygenase. This enzyme catalyzes the reaction causing the addition of a hydroxyl group to the end of the 6-carbon aromatic ring of phenylalanine, such that it becomes tyrosine.

Metabolism

[edit]
Conversion of phenylalanine and tyrosine to its biologically important derivatives.

Phosphorylation and sulfation

[edit]

Some of the tyrosine residues can be tagged (at the hydroxyl group) with a phosphate group (phosphorylated) by protein kinases. In its phosphorylated form, tyrosine is called phosphotyrosine. Tyrosine phosphorylation is considered to be one of the key steps in signal transduction and regulation of enzymatic activity. Phosphotyrosine can be detected through specific antibodies. Tyrosine residues may also be modified by the addition of a sulfate group, a process known as tyrosine sulfation.[17] Tyrosine sulfation is catalyzed by tyrosylprotein sulfotransferase (TPST). Like the phosphotyrosine antibodies mentioned above, antibodies have recently been described that specifically detect sulfotyrosine.[18]

Precursor to neurotransmitters and hormones

[edit]

In dopaminergic cells in the brain, tyrosine is converted to L-DOPA by the enzyme tyrosine hydroxylase (TH). TH is the rate-limiting enzyme involved in the synthesis of the neurotransmitter dopamine. Dopamine can then be converted into other catecholamines, such as norepinephrine (noradrenaline) and epinephrine (adrenaline).

The thyroid hormones triiodothyronine (T3) and thyroxine (T4) in the colloid of the thyroid are also derived from tyrosine.

Biosynthetic pathways for catecholamines and trace amines in the human brain[19][20][21]
Graphic of catecholamine and trace amine biosynthesis
The image above contains clickable links
Tyrosine is a precursor to trace amine compounds and the catecholamines.


Precursor to other compounds

[edit]

The latex of Papaver somniferum, the opium poppy, has been shown to convert tyrosine into the alkaloid morphine and the bio-synthetic pathway has been established from tyrosine to morphine by using Carbon-14 radio-labelled tyrosine to trace the in-vivo synthetic route.[22]Tyrosine ammonia lyase (TAL) is an enzyme in the natural phenols biosynthesis pathway. It transforms L-tyrosine into p-coumaric acid. Tyrosine is also the precursor to the pigment melanin. Tyrosine (or its precursor phenylalanine) is needed to synthesize the benzoquinone structure which forms part of coenzyme Q10.[23][24]

Degradation

[edit]
The decomposition of tyrosine to acetoacetate and fumarate. Two dioxygenases are necessary for the decomposition path. The end products can then enter into the citric acid cycle.

[citation needed]

The decomposition of L-tyrosine (syn. para-hydroxyphenylalanine) begins with an α-ketoglutarate dependent transamination through the tyrosine transaminase to para-hydroxyphenylpyruvate. The positional description para, abbreviated p, mean that the hydroxyl group and side chain on the phenyl ring are across from each other (see the illustration below).

The next oxidation step catalyzes by p-hydroxyphenylpyruvate dioxygenase and splitting off CO2 homogentisate (2,5-dihydroxyphenyl-1-acetate).[25] In order to split the aromatic ring of homogentisate, a further dioxygenase, homogentisate 1,2-dioxygenase is required. Thereby, through the incorporation of a further O2 molecule, maleylacetoacetate is created.

Fumarylacetoacetate is created by maleylacetoacetate cis-trans-isomerase through rotation of the carboxyl group created from the hydroxyl group via oxidation. This cis-trans-isomerase contains glutathione as a coenzyme. Fumarylacetoacetate is finally split by the enzyme fumarylacetoacetate hydrolase through the addition of a water molecule.

Thereby fumarate (also a metabolite of the citric acid cycle) and acetoacetate (3-ketobutyroate) are liberated. Acetoacetate is a ketone body, which is activated with succinyl-CoA, and thereafter it can be converted into acetyl-CoA, which in turn can be oxidized by the citric acid cycle or be used for fatty acid synthesis.

Phloretic acid is also a urinary metabolite of tyrosine in rats.[26]

Ortho- and meta-tyrosine

[edit]
Enzymatic oxidation of tyrosine by phenylalanine hydroxylase (top) and non-enyzmatic oxidation by hydroxyl free radicals (middle and bottom).

Three structural isomers of L-tyrosine are known. In addition to the common amino acid L-tyrosine, which is the para isomer (para-tyr, p-tyr or 4-hydroxyphenylalanine), there are two additional regioisomers, namely meta-tyrosine (also known as 3-hydroxyphenylalanine, L-m-tyrosine, and m-tyr) and ortho-tyrosine (o-tyr or 2-hydroxyphenylalanine), that occur in nature. The m-tyr and o-tyr isomers, which are rare, arise through non-enzymatic free-radical hydroxylation of phenylalanine under conditions of oxidative stress.[27][28]

Medical use

[edit]

Tyrosine is a precursor to neurotransmitters and increases plasma neurotransmitter levels (particularly dopamine and norepinephrine),[29] but has little if any effect on mood in normal subjects.[30][31][32]

A 2015 systematic review found that "tyrosine loading acutely counteracts decrements in working memory and information processing that are induced by demanding situational conditions such as extreme weather or cognitive load" and therefore "tyrosine may benefit healthy individuals exposed to demanding situational conditions".[33]

Industrial synthesis

[edit]

L-Tyrosine is used in pharmaceuticals, dietary supplements, and food additives. Two methods were formerly used to manufacture L-tyrosine. The first involves the extraction of the desired amino acid from protein hydrolysates using a chemical approach. The second utilizes enzymatic synthesis from phenolics, pyruvate, and ammonia through the use of tyrosine phenol-lyase.[34] Advances in genetic engineering and the advent of industrial fermentation have shifted the synthesis of L-tyrosine to the use of engineered strains of E. coli.[35][34]

See also

[edit]

References

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

Tyrosine

View on Grokipedia
from Grokipedia
Tyrosine is a nonessential with the chemical formula C₉H₁₁NO₃, featuring an aromatic with a phenolic hydroxyl group that imparts polarity and UV absorption properties. It is encoded by the codons UAU and UAC in the and is synthesized in the body from via the enzyme . This is classified as conditionally essential, meaning dietary intake may be required under conditions of physiological stress or deficiency in phenylalanine metabolism. In biochemical pathways, tyrosine plays a pivotal role as a precursor to key catecholamines, including the neurotransmitters , norepinephrine, and epinephrine, which are essential for neural signaling and stress responses. It is also critical for the synthesis of such as thyroxine (T4) and (T3), which regulate , growth, and development. Additionally, tyrosine contributes to production, the pigment responsible for coloration in , , and eyes, through its conversion to dopaquinone. Within proteins, tyrosine's phenolic side chain enables hydrogen bonding and hydrophobic interactions that stabilize three-dimensional structures, while its hydroxyl group serves as a target for by tyrosine kinases, a modification central to , regulation, and pathways like insulin and responses. Due to its physicochemical properties, tyrosine facilitates molecular recognition and is often found at protein interfaces or active sites.

Chemical Properties

Structure and Nomenclature

Tyrosine is an α-amino acid with the molecular formula C₉H₁₁NO₃. Its structure consists of a central chiral α-carbon atom bonded to an amino group (-NH₂), a carboxyl group (-COOH), a , and a known as the R-group. The R-group is a 4-hydroxybenzyl moiety, which features a phenyl ring with a hydroxyl (-OH) group attached at the para position, connected via a methylene (-CH₂-) bridge to the α-carbon, effectively forming a modified backbone with an aromatic phenolic substituent. The systematic IUPAC name for the naturally occurring form is (2S)-2-amino-3-(4-hydroxyphenyl)propanoic acid. In biochemical contexts, tyrosine is commonly abbreviated as Tyr (three-letter code) or Y (one-letter code) when representing its residue in protein sequences. The compound is also referred to as L-tyrosine to specify its enantiomeric configuration, distinguishing it from the synthetic D-tyrosine. Tyrosine was first isolated in 1846 from the milk protein by German chemist through alkaline . The name "tyrosine" derives from the Greek word tyros, meaning cheese, reflecting its origin in dairy-derived . Regarding , the biologically relevant is L-tyrosine, which has the (S) configuration at the α-carbon according to the Cahn-Ingold-Prelog priority rules. This L-form exhibits levorotatory optical activity, with a of [α]_D^{22} = -10.6° (measured in a 4% solution in 1 N HCl). The D-enantiomer, with (R) configuration, is not utilized in standard and shows opposite .

Physical and Chemical Characteristics

Tyrosine appears as a crystalline or powder, odorless and stable under normal conditions. It has a of approximately 343 °C, at which it decomposes without boiling. in is low, approximately 0.45 g/L (or 0.45 mg/mL) at 25 °C, though it increases in alkaline solutions; it is insoluble in nonpolar solvents like , , and acetone. Chemically, tyrosine is an α-amino acid with three ionizable groups, exhibiting pKa values of 2.20 for the carboxyl group, 9.11 for the amino group, and 10.07 for the phenolic hydroxyl group on its aromatic . At physiological (around 7), it exists predominantly as a with the carboxyl and amino groups ionized, while the phenolic group remains protonated. The aromatic enables strong absorbance at 274 nm with a molar extinction coefficient of 1405 M⁻¹ cm⁻¹ in phosphate buffer ( 7), useful for spectrophotometric detection. The polar hydroxyl group facilitates hydrogen bonding, contributing to its reactivity in chemical and biochemical contexts. Tyrosine demonstrates sensitivity to oxidation, particularly under alkaline conditions or in the presence of metal ions and oxidants like , leading to products such as dopaquinone. This reactivity arises from the phenolic moiety, which can undergo one-electron oxidation to form a tyrosyl radical. For identification, tyrosine's spectroscopic characteristics include ¹H NMR signals for the aromatic protons at approximately 6.8–7.2 ppm (doublets) in D₂O, the methylene protons at 2.9–3.1 ppm (doublet of doublets), and the methine proton at 4.0 ppm (triplet); the ¹³C NMR shows the phenolic carbon at around 155 ppm and aromatic carbons between 115–130 ppm. reveals key absorption bands at 3300–3500 cm⁻¹ (O-H and N-H stretching), 1600–1700 cm⁻¹ (C=O stretch), and 1400–1500 cm⁻¹ (aromatic C=C).

Biological Role

Functions in Proteins

Tyrosine is one of the 20 standard encoded by the , specifically by the codons UAU and UAC, and is incorporated into polypeptide chains during protein synthesis. In the human , tyrosine accounts for approximately 3.2% of all residues, reflecting its moderate abundance across diverse protein types. The hydrophilic of tyrosine, consisting of a benzyl ring with a para-hydroxyl group, plays a key role in by forming hydrogen bonds that promote proper folding and enhance thermodynamic stability. These hydrogen bonds, often involving the phenolic hydroxyl, contribute favorably to overall protein integrity, even in the absence of direct intramolecular pairing with other residues. The aromatic ring further enables pi-stacking interactions with other aromatic like and , which help stabilize secondary and tertiary structures through non-covalent stacking of electron clouds. Tyrosine's phenolic moiety also facilitates coordination with metal ions via its oxygen atom, particularly when deprotonated to form a phenolate, which is essential for catalytic functions in metalloproteins. In enzyme active sites, tyrosine residues often position the hydroxyl group to act as a or donor/acceptor for substrate binding; a notable example is Tyr122 in the A subunit of Escherichia coli , which forms a transient covalent phosphotyrosyl-DNA intermediate during strand breakage and rejoining. In structural proteins such as and , tyrosine supports cross-linking potential through its reactive phenol group, contributing to the mechanical strength and elasticity of extracellular matrices. Beyond these static roles, tyrosine residues in proteins like receptor tyrosine kinases serve as sites for post-translational , enabling dynamic signaling cascades, though such modifications are addressed separately.

Post-Translational Modifications

Tyrosine residues in proteins undergo several key post-translational modifications (PTMs) that leverage the reactivity of their phenolic hydroxyl group, enabling dynamic regulation of protein function, particularly in cellular signaling and interactions. These modifications include , sulfation, , and , each catalyzed by specific enzymes or reactive species and occurring in distinct cellular contexts. Phosphorylation is the most extensively studied PTM of tyrosine, involving the covalent addition of a group to the hydroxyl oxygen by protein tyrosine s (PTKs), such as the non-receptor Src. This reversible modification is central to , where it creates docking sites for downstream effectors containing SH2 or PTB domains, thereby propagating signals from cell surface receptors to intracellular pathways. The reaction is catalyzed as follows: Tyr-OH+ATP→Tyr-O-PO32−+ADP\text{Tyr-OH} + \text{ATP} \rightarrow \text{Tyr-O-PO}_3^{2-} + \text{ADP} Dephosphorylation by protein tyrosine phosphatases (PTPs) ensures tight temporal control. Tyrosine sulfation, mediated by tyrosylprotein sulfotransferases (TPSTs) in the trans-Golgi network of the secretory pathway, introduces a group to the hydroxyl oxygen using (PAPS) as the donor. This modification enhances protein-protein interactions, such as those between and their receptors or in coagulation factors, influencing processes like and . Sulfation occurs on secreted or proteins and is irreversible, with TPST-1 and TPST-2 exhibiting distinct substrate preferences. Nitration of tyrosine forms 3-nitrotyrosine through the reaction of the phenolic ring with (ONOO⁻), a potent oxidant generated from and under conditions of . This non-enzymatic modification serves as a for nitro-oxidative damage in diseases like , neurodegeneration, and cardiovascular disorders, as it impairs protein function by altering tyrosine's hydrogen bonding and phosphorylation potential. Detection of elevated 3-nitrotyrosine levels in tissues correlates with peroxynitrite-mediated . Halogenation, specifically iodination, targets tyrosine residues in within thyroid follicular cells, where catalyzes the addition of iodine atoms to form mono- and diiodotyrosine, which then couple to produce triiodothyronine (T3) and thyroxine (T4). This modification is essential for hormone synthesis, regulated by (TSH), and occurs in the of the gland. Deficiencies in iodination lead to . These PTMs collectively regulate critical signaling cascades, such as the (MAPK) pathway, where on receptor tyrosine kinases initiates ERK, JNK, and p38 activation in response to growth factors. In eukaryotes, approximately 2% of events target tyrosine residues, underscoring its specificity despite lower abundance compared to serine/ sites. Dysregulation of these modifications contributes to oncogenesis, immune disorders, and metabolic diseases.

Nutrition and Sources

Dietary Requirements

Tyrosine is classified as a non-essential in humans, as it can be endogenously synthesized from the essential via the enzyme . However, it becomes conditionally essential during periods of physiological stress, such as illness or trauma, when synthesis may not meet demands, or in cases of deficiency from low-protein diets. It is also essential for individuals with (PKU), a impairing hydroxylation, necessitating dietary tyrosine supplementation to prevent neurological complications. When phenylalanine intake is adequate, the estimated average requirement for tyrosine is approximately 6 mg per kg of body weight per day for healthy adults, ensuring provision for protein synthesis and neurotransmitter production. When considered together with phenylalanine, the combined requirement is 25 mg per kg of body weight per day or 30 mg per g of dietary protein, aligning with patterns for optimal protein quality as per the 2007 WHO/FAO/UNU report. These values derive from indicator amino acid oxidation studies balancing nitrogen retention and metabolic needs. For infants and children, requirements scale with growth rates, while pregnant individuals may need up to 36 mg/kg/day combined to support fetal development. Dietary tyrosine is absorbed primarily in the through neutral transporters, notably LAT1 (SLC7A5), a sodium-independent exchanger in the system L family that handles large neutral . This process is competitive; elevated levels of competing substrates like , , , , or can inhibit tyrosine uptake, potentially affecting during high-protein meals. Once absorbed, tyrosine enters the portal circulation for distribution to tissues. True tyrosine deficiency is rare in well-nourished populations due to its synthesis from but can arise from chronic low-protein intake or unmanaged PKU, leading to symptoms such as , depressed mood, and . These effects stem from reduced production of catecholamine neurotransmitters like and norepinephrine, which rely on tyrosine as a precursor and influence , , and stress response. In severe cases, prolonged deficiency may exacerbate cognitive impairments. The / (WHO/FAO) standards, last comprehensively updated in 2013 with ongoing refinements through 2023 expert consultations, maintain the combined + tyrosine requirement at 30 mg/g for adults but highlight elevated tyrosine needs in PKU patients—typically 40–120 mg/kg/day depending on age—to compensate for restricted and support neurometabolic balance. These guidelines emphasize monitoring plasma levels to avoid both deficiency and excess, which could lead to hyperphenylalaninemia.

Food Sources

Foods rich in tyrosine, such as eggs, chicken, almonds, bananas, avocados, beans, and dark chocolate, provide dietary tyrosine that supports its role as a precursor to neurotransmitters like dopamine. Tyrosine is abundant in protein-rich foods, with animal-derived sources generally providing higher concentrations per serving compared to plant-based options. Notable animal sources include products such as cheese, which contains approximately 2.0 g of tyrosine per 100 g, and eggs, offering about 0.5 g per 100 g. Meats like and also contribute significantly, with lean providing around 1.2 g per 100 g and chicken breast approximately 1.1 g per 100 g. Plant-based foods serve as viable sources, particularly for vegetarians and vegans, though they often require larger portions to match animal-derived intake levels. Soy products stand out, with roasted soybeans delivering about 1.8 g per 100 g and around 0.8 g per 100 g. Seeds and nuts are also rich; for instance, contain roughly 1.2 g per 100 g, while sesame seeds provide 0.9 g per 100 g. Legumes like lentils and beans offer 0.6–0.7 g per 100 g, and whole grains such as contribute about 0.5 g per 100 g.
Food CategoryExampleTyrosine Content (g/100 g)Source
Parmesan cheese2.0USDA FoodData Central
EggsWhole egg, cooked0.5USDA FoodData Central
/Lean 1.2USDA FoodData Central
Roasted soybeans1.8USDA FoodData Central
seeds1.2USDA FoodData Central
The of tyrosine varies by source, with animal proteins exhibiting higher digestibility (typically 90–95%) due to their complete profiles, allowing more efficient absorption in the . In contrast, plant proteins often have lower (around 70–85%) owing to factors like higher content and anti-nutritional compounds such as phytates, which can bind and reduce uptake; vegetarian diets may thus benefit from combining tyrosine-rich plants with sources to optimize overall balance. Food processing impacts tyrosine availability minimally in terms of , as the is heat-resistant and does not degrade significantly during cooking or . However, in foods with high or , processing methods like milling or soaking can enhance by reducing these inhibitors, whereas overprocessing (e.g., excessive heating) may slightly lower protein digestibility in some cases. Tyrosine is also available as a in the form of L-tyrosine powder or capsules, commonly used to supplement intake beyond food sources, with typical doses ranging from 500 to 2000 mg per day taken between meals. In the average Western diet, daily tyrosine intake ranges from 1 to 3 g, primarily derived from protein consumption, aligning with or exceeding the estimated adult requirement of about 25 mg per kg body weight when combined with ; this is supported by data from nutritional surveys using the USDA database updated through 2024.

Biosynthesis

Pathway in Organisms

In mammals, including humans, the primary pathway for endogenous tyrosine production involves the of the L-phenylalanine by the (PAH), which serves as the committed and rate-limiting step in this conversion. PAH catalyzes the insertion of a hydroxyl group into the aromatic ring of L-phenylalanine, utilizing molecular oxygen (O₂) and the cofactor (6R)-L-erythro-5,6,7,8-tetrahydrobiopterin (BH₄) to produce L-tyrosine, , and quinonoid dihydrobiopterin (qBH₂). The reaction can be represented as: L-Phe+O2+BH4→L-Tyr+H2O+qBH2\text{L-Phe} + \text{O}_2 + \text{BH}_4 \rightarrow \text{L-Tyr} + \text{H}_2\text{O} + \text{qBH}_2 This process occurs predominantly in the of hepatocytes in the liver, with significant contributions from the , where it accounts for net tyrosine release into the systemic circulation. The is modulated by substrate availability, with acting as an allosteric activator to enhance PAH activity under physiological conditions. In healthy adults, the daily flux through this pathway approximates 1–2 g of tyrosine synthesized, varying with dietary intake and supporting overall . This PAH-dependent pathway exhibits evolutionary conservation across diverse organisms, with homologs of PAH identified in bacteria such as and , where they similarly facilitate phenylalanine hydroxylation for tyrosine production, underscoring an ancient origin predating eukaryotic diversification. Defects in human PAH, often due to impairing function or BH₄ cofactor regeneration, lead to (PKU), an autosomal recessive disorder characterized by hyperphenylalaninemia and impaired tyrosine synthesis, necessitating to prevent neurological damage. In contrast, prokaryotes and employ alternative routes for tyrosine biosynthesis that do not rely on PAH but instead branch from the , a seven-step anabolic sequence absent in animals. Chorismate is converted to prephenate by chorismate mutase. In the predominant pathway in , prephenate is transaminated to arogenate, which is then dehydrogenated to L-tyrosine via . Alternatively, in some prokaryotes and , prephenate undergoes oxidative to 4-hydroxyphenylpyruvate via prephenate , followed by to L-tyrosine. These microbial and plant-specific pathways highlight the divergence in metabolism across kingdoms.

Regulation of Synthesis

The biosynthesis of tyrosine in mammals primarily occurs through the hydroxylation of by the enzyme (PAH), which requires the cofactor (BH4) for activity. Enzymatic regulation of this process involves allosteric activation of PAH by , its substrate, which enhances the enzyme's catalytic efficiency at physiological concentrations, while high levels of BH4 can modulate this activation to prevent excessive activity. Additionally, BH4 is recycled after oxidation to quinonoid-dihydrobiopterin (qBH2) during the reaction, a process mediated by dihydropteridine reductase (DHPR), ensuring sustained cofactor availability and preventing accumulation of inhibitory oxidized forms like 7,8-dihydrobiopterin (BH2). Disruptions in BH4 recycling, such as DHPR deficiency, can impair tyrosine synthesis even with functional PAH. Genetic factors play a critical role in regulating tyrosine synthesis, as in the PAH gene on lead to (PKU), an autosomal recessive disorder characterized by deficient PAH activity and consequent hyperphenylalaninemia. Over 1,000 PAH variants have been identified, ranging from complete loss-of-function in classic PKU to milder alleles in non-classic forms, with varying by and , estimated at approximately 1 in 10,000 to 15,000 live births in populations of European and East Asian descent, and a global average of about 1 in 24,000 live births. These genetic alterations reduce PAH expression or stability, thereby limiting tyrosine production and highlighting the enzyme's central regulatory role in . Hormonal influences further modulate PAH activity and expression. and catecholamines, such as epinephrine, upregulate PAH through cAMP-dependent , increasing enzymatic rates during or stress states to promote disposal. In contrast, insulin downregulates PAH activity, suppressing and reducing tyrosine synthesis in fed states to balance amino acid flux toward anabolic pathways. Dietary factors also contribute, as elevated intake from high-protein meals induces PAH via transcriptional activation, adapting hepatic capacity to handle substrate load without toxicity. Recent has explored therapeutic modulation of these regulatory mechanisms, particularly for partial PAH defects. Studies in demonstrated that BH4 supplementation (as sapropterin dihydrochloride) enhances residual PAH activity in responsive PKU patients with milder mutations, reducing blood by up to 30% and improving tyrosine production without full dietary restriction, though long-term efficacy varies by .

Precursor to Neurotransmitters and Hormones

Tyrosine serves as the primary precursor for the biosynthesis of catecholamines, a group of neurotransmitters and hormones that include dopamine, norepinephrine, and epinephrine. The pathway begins with the rate-limiting step catalyzed by tyrosine hydroxylase (TH), an enzyme predominantly expressed in catecholaminergic neurons of the central and peripheral nervous systems, as well as in the adrenal medulla. TH converts L-tyrosine to L-3,4-dihydroxyphenylalanine (L-DOPA) in a reaction requiring molecular oxygen (O₂), ferrous iron (Fe²⁺), and tetrahydrobiopterin (BH₄) as a cofactor: L-tyrosine+O2+BH4→L-DOPA+H2O+qBH2\text{L-tyrosine} + \text{O}_2 + \text{BH}_4 \rightarrow \text{L-DOPA} + \text{H}_2\text{O} + \text{qBH}_2 where qBH₂ is the quinonoid dihydrobiopterin intermediate, which is subsequently regenerated to BH₄ by pterin-4α-carbinolamine dehydratase and dihydropteridine reductase. L-DOPA is then decarboxylated to dopamine by aromatic L-amino acid decarboxylase (AADC, also known as DOPA decarboxylase), a pyridoxal phosphate (PLP)-dependent enzyme widely distributed in the brain and periphery: L-DOPA→dopamine+CO2\text{L-DOPA} \rightarrow \text{dopamine} + \text{CO}_2 Dopamine functions as a neurotransmitter in specific brain regions but serves as an intermediate for further synthesis in noradrenergic and adrenergic cells. In these cells, dopamine is transported into synaptic vesicles or chromaffin granules and hydroxylated to norepinephrine by dopamine β-hydroxylase (DBH), which requires molecular oxygen, ascorbic acid (as a reducing agent), and copper (Cu²⁺) as cofactors: dopamine+O2+ascorbate→norepinephrine+H2O+dehydroascorbate\text{dopamine} + \text{O}_2 + \text{ascorbate} \rightarrow \text{norepinephrine} + \text{H}_2\text{O} + \text{dehydroascorbate} DBH is localized within the vesicles of noradrenergic neurons and adrenal chromaffin cells. Finally, in the , norepinephrine is methylated to epinephrine by phenylethanolamine N-methyltransferase (PNMT), using S-adenosylmethionine (SAM) as the methyl donor: norepinephrine+SAM→epinephrine+S-adenosylhomocysteine\text{norepinephrine} + \text{SAM} \rightarrow \text{epinephrine} + \text{S-adenosylhomocysteine} PNMT is expressed in the of chromaffin cells in the . Only a small fraction of total tyrosine in humans is utilized for catecholamine synthesis, with the majority incorporated into proteins. In addition to catecholamines, tyrosine is essential for the production of (T3) and thyroxine (T4). This process occurs in the gland, where tyrosine residues within the protein are iodinated by (TPO), an enzyme located on the apical of follicular cells facing the . TPO catalyzes the oxidation of (I⁻) to iodine (I₂) using (H₂O₂), enabling sequential iodination to form monoiodotyrosine (MIT) and diiodotyrosine (DIT). Subsequent oxidative coupling reactions, also mediated by TPO, link these iodotyrosines: one MIT and one DIT form T3, while two DIT molecules couple to produce T4. These hormones remain bound to for storage until releases them into circulation. The catecholamines and derived from tyrosine play critical roles in regulating mood, cognition, and the stress response. and norepinephrine modulate reward, attention, and arousal, while epinephrine and norepinephrine mediate the , increasing heart rate and energy mobilization. influence basal metabolism, growth, and neural development. Deficiencies in tyrosine availability or disruptions in these pathways, such as reduced catecholamine synthesis, have been linked to depressive symptoms and impaired stress resilience, as acute depletion of tyrosine lowers mood and cognitive under demanding conditions.

Precursor to Pigments and Other Compounds

Tyrosine serves as the primary precursor for synthesis, a process critical for pigmentation in , , and eyes. The pathway begins with the oxidation of L-tyrosine to by the enzyme , followed by further oxidation to dopaquinone. Dopaquinone then cyclizes and polymerizes into eumelanin (black-brown ) or, in the presence of , reacts to form pheomelanin (yellow-red ). This tyrosinase-catalyzed reaction is rate-limiting and occurs in melanosomes of melanocytes. provides photoprotection by absorbing radiation, preventing DNA damage in underlying tissues. In , tyrosine is decarboxylated to , which acts as a precursor for various alkaloids, including alkaloids such as those in the biosynthesis pathway in opium poppy. Tyrosine aminotransferase converts tyrosine to 4-hydroxyphenylpyruvate, which is further transformed into precursors like (S)-norcoclaurine, the foundational unit for these alkaloids. These tyrosine-derived compounds contribute to plant defense mechanisms against herbivores and pathogens. Tyrosine also contributes to the biosynthesis of (ubiquinone), a vital carrier in the mitochondrial respiratory chain. In mammals, tyrosine is degraded to via intermediates like 4-hydroxyphenylpyruvate, which serves as the aromatic head group for CoQ10 and subsequent modifications. This pathway underscores tyrosine's role in cellular energy production and antioxidant defense. Through oxidative processes, tyrosine forms dityrosine cross-links in structural proteins like , enhancing mechanical stability and resistance to . Peroxidases or catalyze the coupling of tyrosine residues, creating covalent bonds that stabilize extracellular matrices in tissues such as skin and . This cross-linking is particularly prominent in aging or stressed . In , tyrosine influences the production of siderophores like enterobactin, a catecholate compound that chelates iron under limiting conditions. Elevated tyrosine levels stimulate enterobactin synthesis in by supporting metabolism linked to the synthetase pathway, aiding bacterial iron acquisition and . The synthesis pathway from tyrosine represents an ancient evolutionary adaptation for protection, conserved across fungi, invertebrates, and vertebrates to shield against solar radiation-induced damage. This primordial role likely drove the selection of tyrosinase-like enzymes in early eukaryotes, facilitating in sun-exposed environments.

Degradation and Catabolism

Tyrosine is primarily catabolized in humans via the fumarylacetoacetate pathway, a series of enzymatic reactions that occur mainly in the of hepatocytes and renal cells, converting the into intermediates that feed into central metabolic pathways for production. This process handles the breakdown of tyrosine derived from dietary intake and , with an estimated daily rate of approximately 50–100 mg/kg body weight in adults. The pathway initiates with the of L-tyrosine to 4-hydroxyphenylpyruvate, catalyzed by the pyridoxal phosphate-dependent tyrosine aminotransferase (TAT; EC 2.6.1.5), using α-ketoglutarate as the amino group acceptor to produce glutamate. Next, 4-hydroxyphenylpyruvate dioxygenase (HPD; EC 1.13.11.27), a non-heme iron and ascorbate-dependent , facilitates the decarboxylative of 4-hydroxyphenylpyruvate, yielding homogentisate and releasing CO₂. The critical ring-opening step follows, where homogentisate 1,2-dioxygenase (HGD; EC 1.13.11.5), a Fe(II)-dependent extradiol dioxygenase, cleaves the aromatic ring of homogentisate using molecular oxygen: 2,5-dihydroxyphenylacetate (homogentisate)+O2→(2Z,4Z)-hexadienedioate (maleylacetoacetate)\text{2,5-dihydroxyphenylacetate (homogentisate)} + \text{O}_2 \rightarrow (2Z,4Z)\text{-hexadienedioate (maleylacetoacetate)} This reaction incorporates both atoms of O₂ into the product, initiating the fragmentation of the benzene ring. Subsequent isomerization by glutathione S-transferase zeta 1/maleylacetoacetate isomerase (GSTZ1/MAAI; EC 5.2.1.2) converts maleylacetoacetate to fumarylacetoacetate, protecting against the formation of toxic quinones. Finally, fumarylacetoacetate hydrolase (FAH; EC 3.7.1.2) hydrolyzes fumarylacetoacetate to fumarate and acetoacetate. The end products contribute to energy metabolism: fumarate directly enters the tricarboxylic acid (TCA) cycle as a glucogenic intermediate, ultimately yielding ATP through oxidative phosphorylation, while acetoacetate serves as a ketogenic substrate that can be activated to acetoacetyl-CoA and cleaved to two molecules of acetyl-CoA for TCA entry or ketone body formation during fasting. This catabolic route ensures efficient disposal of tyrosine, preventing accumulation that could lead to metabolic imbalance. Defects in pathway enzymes underlie hereditary tyrosinemias: type I results from FAH deficiency, causing toxic buildup of fumarylacetoacetate and succinylacetone leading to liver and kidney failure; type II from TAT deficiency, manifesting as corneal and palmoplantar lesions; and type III from HPD deficiency, typically presenting with mild neurological symptoms and elevated tyrosine levels. A related disorder, alkaptonuria, arises from HGD deficiency, resulting in homogentisate accumulation that oxidizes and polymerizes in connective tissues, producing ochronotic pigments responsible for bluish-black discoloration, arthropathy, and cardiovascular complications due to oxidative stress and protein modification.

Ortho- and Meta-Tyrosine

Ortho-tyrosine (o-tyrosine), also known as 2-hydroxyphenylalanine, is a non-natural isomer of tyrosine formed through the non-enzymatic hydroxylation of phenylalanine by hydroxyl radicals during oxidative stress. This reaction targets the ortho position on the benzyl ring of phenylalanine, yielding o-tyrosine as a stable product that serves as a specific biomarker for protein oxidation and hydroxyl radical-mediated damage in biological systems. Unlike the standard para-tyrosine (p-tyrosine), o-tyrosine exhibits altered chemical reactivity, including a propensity for its tyrosyl radical to react preferentially with water, leading to the formation of quinone derivatives rather than typical dimerization pathways observed in p-tyrosine. Due to its positional isomerism, o-tyrosine is rarely incorporated into proteins and disrupts normal protein function when present, contributing to cellular dysfunction under stress conditions. In biological contexts, o-tyrosine accumulates in tissues exposed to , where it reflects cumulative oxidative damage from radiolytic hydroxyl radical generation. For instance, studies on gamma-irradiated animal tissues, such as muscle, demonstrate linear dose-dependent formation of o-tyrosine from endogenous , highlighting its utility as an indicator of . Elevated o-tyrosine levels have also been observed in conditions of chronic , including aging and , where it correlates with disease severity, such as in patients and degeneration. Meta-tyrosine (m-tyrosine), or 3-hydroxyphenylalanine, is another abnormal produced primarily in certain , particularly grasses like , as a non-protein under environmental stress. Its occurs through specialized pathways in root tissues, potentially involving modifications to metabolism, and it is exuded into the as an allelochemical. Chemically, m-tyrosine shares the phenolic hydroxyl group with p-tyrosine but features at the meta position, which shifts its pKa values slightly and enhances its reactivity in oxidative environments, though it remains uncommon in protein structures due to its non-standard incorporation. In , m-tyrosine acts as a defense signal by inhibiting the growth of competing through herbicidal effects, disrupting their protein synthesis and metabolic processes upon uptake. Detection of both o-tyrosine and m-tyrosine typically employs coupled with (HPLC-MS), allowing sensitive quantification at picogram levels in complex biological matrices like plasma, tissues, or plant exudates. These methods often use for accuracy, revealing elevated concentrations of m-tyrosine in stressed plant roots and o-tyrosine in inflammatory or aged samples, underscoring their roles as indicators of oxidative and environmental stress.

D-Tyrosine and Other Isomers

D-Tyrosine, the mirror-image of the naturally abundant L-tyrosine, is rarely incorporated into eukaryotic proteins but plays specialized roles in prokaryotic structures and certain bioactive peptides. Exogenous D-tyrosine can be incorporated into the layer of bacterial cell walls, where it modulates remodeling by inhibiting formation and disrupting cross-linking during growth and division. The conversion between L- and D-tyrosine occurs through , which can be either enzymatic, mediated by racemases, or spontaneous via non-enzymatic at the alpha-carbon under physiological conditions. Enzymatic racemization facilitates the production of D-tyrosine in microbial environments, while spontaneous processes lead to its gradual accumulation in long-lived proteins of aging tissues, such as lens crystallins and proteins, potentially contributing to age-related and dysfunction. Beyond stereoisomers, other tyrosine isomers include β-tyrosine, an uncommon variant where the amino group is attached to the β-carbon rather than the α-carbon, produced as a in certain plants like through the action of tyrosine aminomutase enzymes. β-Tyrosine participates in specialized metabolic pathways, such as defense compound , but is not a standard component of protein synthesis. Alloisomers, such as those arising from epimerization at other chiral centers, occasionally emerge in metabolic intermediates but remain marginal in biological contexts. In the mammalian brain, D-tyrosine exerts signaling effects primarily through its metabolism by D-amino acid oxidase (DAAO), an that oxidizes it to reactive species, influencing neuronal excitability and potentially modulating N-methyl-D-aspartate receptor (NMDAR) activity indirectly via altered states. This pathway links D-tyrosine to cognitive processes, with dysregulation implicated in neurological conditions. In , D-tyrosine functions as a quorum-sensing signal that inhibits formation by disrupting cross-linking and matrix production, effective at nanomolar concentrations across Gram-positive and Gram-negative , thereby preventing persistent infections. Additionally, radiolabeled D-tyrosine has been investigated as a bacteria-specific probe for (PET) imaging of active infections (as of 2024). Detection of D-tyrosine and its isomers relies on chiral separation techniques, such as (HPLC) with chiral stationary phases, which resolve enantiomers based on differential interactions with optically active columns, enabling precise quantification in biological samples like serum and . Recent studies using these methods have explored levels, including D-tyrosine, in psychiatric disorders, highlighting potential roles.

Clinical and Therapeutic Aspects

Metabolic Disorders

Tyrosinemia refers to a group of rare genetic disorders caused by defects in the metabolism of tyrosine, leading to its accumulation and toxic effects on various organs. These autosomal recessive conditions primarily affect the liver, kidneys, skin, and eyes, with symptoms varying by type depending on the specific deficiency in the tyrosine catabolic pathway. , the most severe form, results from a deficiency in fumarylacetoacetate (FAH), the final in tyrosine degradation, causing buildup of toxic metabolites like succinylacetone that damage the liver and kidneys. Symptoms typically emerge in infancy and include , renal tubular dysfunction with , , , and neurological crises resembling , potentially leading to death without intervention. The condition is diagnosed through elevated succinylacetone in urine and confirmed by FAH gene . Treatment involves (2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione), an inhibitor of upstream 4-hydroxyphenylpyruvate dioxygenase approved by the FDA in 2002, combined with a low-tyrosine and low-phenylalanine diet to prevent metabolite accumulation and tyrosine elevation. remains an option for cases unresponsive to medical therapy. Tyrosinemia type II, also known as oculocutaneous tyrosinemia or Richner-Hanhart syndrome, stems from a deficiency in hepatic tyrosine aminotransferase (TAT), the first in tyrosine , resulting in elevated plasma tyrosine levels that crystallize in tissues. Clinical manifestations, often appearing in , include painful corneal erosions and ulcers leading to and potential vision impairment, as well as palmoplantar —thickened, hyperkeratotic skin lesions on the palms and soles that cause discomfort and secondary infections. Neurological symptoms such as or behavioral issues may occur in some cases. Management focuses on a strict low-tyrosine diet to normalize plasma levels and alleviate symptoms, with no specific pharmacologic replacement available. Tyrosinemia type III is caused by mutations in the HPD gene encoding 4-hydroxyphenylpyruvate dioxygenase, an midway in the tyrosine degradation pathway, leading to mild hypertyrosinemia and excretion of 4-hydroxyphenylpyruvate and its derivatives in urine. This rare form presents with variable, often mild symptoms, primarily neurological, including intermittent , tremors, seizures, and mild , though some individuals remain . Unlike types I and II, liver and kidney involvement is minimal, and the condition is managed with dietary tyrosine restriction if symptoms manifest. Phenylketonuria (PKU), while primarily a disorder of metabolism due to (PAH) deficiency, indirectly affects levels by impairing the conversion of to , resulting in secondary deficiency that may contribute to neuropsychological impairments in untreated patients. Diagnosis of types I-III relies on programs, which measure elevated or succinylacetone in blood spots via , enabling early detection before symptoms appear. Incidence varies: type I occurs in approximately 1 in 100,000 births worldwide, though higher in certain populations like (1 in 16,000); type II in fewer than 1 in 250,000; and type III in under 1 in 1,000,000. Confirmatory testing includes enzyme assays, metabolite profiling, and genetic analysis of FAH, TAT, or HPD genes. As of 2025, trials for type I, using lentiviral vectors or CRISPR/Cas9 to deliver functional FAH, show promising preclinical efficacy in restoring enzyme activity and preventing . For example, lentiviral-based approaches have demonstrated nearly complete liver repopulation in pig models within 9–12 months.

Medical and Supplemental Uses

Tyrosine supplementation has been investigated for its potential to mitigate cognitive impairments under stressful conditions, such as or high-pressure environments. Human studies provide the strongest evidence for L-tyrosine's nootropic effects in preventing cognitive decline during acute stressors, including cold exposure, sleep deprivation, noise, altitude, or intense training; benefits occur primarily under these demanding conditions, not in rested states. The most consistent effective dose is 100–150 mg/kg body weight, administered about 60 minutes prior to the stressor (e.g., 7–10.5 g for a 70 kg person or 9–13.5 g for a 90 kg person); some studies use split doses (e.g., two doses 30–60 minutes apart) to improve tolerance, while lower fixed doses (e.g., 2 g) show milder benefits in specific contexts like combat training. Studies from the 1980s, including U.S. Army research, demonstrated that tyrosine administration improved , reaction time, and overall performance in during simulated and sustained , likely by replenishing catecholamine neurotransmitters depleted by stress. A 2 g daily dose over five days, for example, enhanced and reduced fatigue in demanding exercises. In the management of (PKU), is supplemented as part of -restricted diets because the condition impairs its endogenous production, making it conditionally essential to prevent deficiencies that could affect synthesis and neurodevelopment. Recommended intakes for children with classical PKU are at least five times those of to maintain plasma levels within 30–60 μmol/L, often achieved through specialized mixtures. Conversely, in tyrosinemia type 1, dietary guidelines emphasize restriction alongside therapy to control elevated levels and prevent liver and kidney damage, using low- formulas to keep plasma concentrations below 500 μmol/L. Tyrosine serves as the immediate biochemical precursor to (levodopa), the standard pharmacological treatment for , where it is converted via to replenish in the . Levodopa administration bypasses the rate-limiting step in catecholamine synthesis, alleviating motor symptoms like bradykinesia and rigidity, though long-term use requires carbidopa to enhance delivery and reduce peripheral side effects. Additionally, inhibitors, such as , target dysregulated s in cancers like chronic and gastrointestinal stromal tumors by competitively binding the ATP site of BCR-ABL and c-KIT kinases, inhibiting uncontrolled . Emerging research explores tyrosine's role in attention-deficit/hyperactivity disorder (ADHD) and depression, with studies indicating potential benefits in boosting and norepinephrine to improve focus and mood, though larger randomized controlled studies are needed for confirmation. For instance, a 2024 study combining tyrosine with L-theanine showed reductions in stress biomarkers and enhancements in cognitive , suggesting adjunctive value in ADHD-like symptoms under acute . In depression, some studies suggest potential benefits in supporting catecholamine pathways for mood improvement, though evidence is mixed and larger studies are needed. Tyrosine supplements are generally recognized as safe by the U.S. at doses up to 12 g per day for short-term use, with no serious adverse effects reported in clinical trials at 100–150 mg/kg body weight. However, contraindications include or , as tyrosine may elevate production and exacerbate symptoms. It is also advised against in individuals with a history of , due to its role in synthesis potentially stimulating pigmented tumor growth.

Production Methods

Biosynthetic Production

Biosynthetic production of L-tyrosine primarily relies on microbial processes, leveraging engineered to overproduce the through the , a key metabolic route for synthesis. In this pathway, phosphoenolpyruvate and erythrose-4-phosphate are converted to chorismate, which then branches to prephenate and ultimately L-tyrosine via enzymes such as prephenate dehydrogenase and arogenate dehydrogenase. Industrial strains are optimized by genetic modifications to deregulate feedback inhibition, enhance precursor supply, and improve carbon flux, enabling high-titer production from glucose or other renewable feedstocks. Engineered strains have been widely developed for L-tyrosine , with strategies including overexpression of genes like aroG (3-deoxy-D-arabino-heptulosonate-7-phosphate synthase) and deletion of competing pathways such as tyrosine repressor (tyrR). Recent advancements have achieved titers up to 92.5 g/L in fed-batch , with yields of approximately 0.266 g/g glucose, demonstrating the scalability of E. coli for commercial applications. Similarly, species, such as C. glutamicum and C. crenatum, are engineered by amplifying the and introducing feedback-resistant enzymes, resulting in efficient L-tyrosine accumulation; for instance, optimized C. crenatum strains produce 34.6 g/L in fed-batch under industrial conditions. As of 2024, efforts in C. crenatum have achieved titers of 34.6 g/L using mixed carbon sources like glucose and . Plant-based methods contribute to L-tyrosine supply through enzymatic of protein-rich sources like soy and corn, yielding hydrolysates from which L-tyrosine can be isolated or further converted. Soy protein isolates are treated with proteases such as Alcalase or to break down globulins into peptides and free , releasing free L-tyrosine from the protein hydrolysates, which can then be purified. Corn hydrolysates similarly undergo enzymatic digestion to release aromatic , with L-tyrosine fractions purified for use; this approach leverages agricultural byproducts for sustainable sourcing. Enzymatic conversion from in these hydrolysates employs hydroxylases to selectively produce L-tyrosine, enhancing yield in integrated bioprocesses. These biosynthetic approaches provide key advantages over traditional chemical methods, including environmental through renewable feedstocks and reduced generation, as well as inherent chiral purity of the L-isomer essential for biological applications. The processes align with principles, minimizing energy-intensive steps and hazardous reagents while supporting models via byproduct utilization. L-Tyrosine produced biosynthetically is commonly used as a to fortify in supplements and feeds, benefiting from its natural origin and high purity. L-tyrosine production remains niche compared to larger-volume amino acids like lysine. This scale supports applications in pharmaceuticals, nutraceuticals, and food industries, with production concentrated in facilities optimized for fermentation efficiency. In the United States, biosynthetically produced L-tyrosine holds Generally Recognized as Safe (GRAS) status from the FDA for use as a nutrient in food products, permitting its addition to formulations under specified conditions without premarket approval, provided it meets purity standards. This regulatory affirmation underscores its safety profile for direct human consumption in dietary supplements and fortified foods.

Chemical Synthesis

The Erlenmeyer-Plöchl azlactone synthesis represents a classic chemical route to DL-tyrosine, involving the condensation of (N-benzoylglycine) with in the presence of to form a 5-(4-hydroxybenzylidene)-2-phenyl-4-oxazolone intermediate, followed by alkaline , acidification, and partial acid to yield the racemic . This method, originally developed in the late and refined for tyrosine production in , provides a straightforward laboratory-scale preparation with overall yields typically around 50-60%. Modern chemical syntheses of tyrosine often employ variants of the Strecker synthesis, where 4-hydroxyphenylacetaldehyde reacts with and to form the α-amino , which is then hydrolyzed under acidic or basic conditions to DL-tyrosine; this approach is valued for its simplicity and use of inexpensive starting materials, achieving yields up to 70% in optimized conditions. For enantioselective production of L-tyrosine, of or dehydroalanine precursors bearing the 4-hydroxyphenyl side chain has become prominent, utilizing chiral or catalysts such as (R)- complexes to deliver the product with enantiomeric excesses exceeding 95%. These catalytic methods enable scalable synthesis with high stereocontrol, as demonstrated in the preparation of tyrosine surrogates where of N-acyl-α,β-dehydroamino acid esters proceeds in >98% ee and 80-90% yield. In industrial contexts, chemical routes like the Strecker variant have historically been used for L-tyrosine production, though biosynthetic alternatives are increasingly competitive due to advantages. Historical advancements include multi-step constructions from phenolic precursors in the mid-20th century, while recent patents explore hybrid chemical-biocatalytic processes, such as combining with enzymatic resolution for yields over 90% in L-tyrosine isolation.

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