Tyrosine
IUPAC name (S)-Tyrosine
Other names L-2-Amino-3-(4-hydroxyphenyl)propanoic acid
Identifiers
CAS number	60-18-4 (L) Y
PubChem	1153
ChemSpider	5833 Y
DrugBank	DB03839
ChEBI	CHEBI:58315 N
ChEMBL	CHEMBL925 Y
Jmol-3D images	Image 1
SMILES N[C@@H](Cc1ccc(O)cc1)C(O)=O
InChI 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 Y Key: OUYCCCASQSFEME-QMMMGPOBSA-N Y
Properties
Molecular formula	C9H11NO3
Molar mass	181.19 g mol−1
Supplementary data page
Structure and properties	n, εr, etc.
Thermodynamic data	Phase behaviour Solid, liquid, gas
Spectral data	UV, IR, NMR, MS
N (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Tyrosine (abbreviated as Tyr or Y)^[1] or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group. The word "tyrosine" is from the Greek tyri, meaning cheese, as it was first discovered in 1846 by German chemist Justus von Liebig in the protein casein from cheese.^[2][3] It is called tyrosyl when referred to as a functional group or side chain.

Functions[link]

Aside from being a proteinogenic amino acid, tyrosine has a special role by virtue of the phenol functionality. It occurs in proteins that are part of signal transduction processes. It functions as a receiver of phosphate groups that are transferred by way of protein kinases (so-called receptor tyrosine kinases). Phosphorylation of the hydroxyl group changes the activity of the target protein.

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 undergoes deprotonation of its phenolic OH-group. This radical is subsequently reduced in the photosystem II by the four core manganese clusters.

Dietary sources[link]

Tyrosine, which can also be synthesized in the body from phenylalanine, is found in many high-protein food products such as chicken, turkey, fish, peanuts, almonds, avocados, milk, cheese, yogurt, cottage cheese, lima beans, pumpkin seeds, sesame seeds, bananas, and soy products.^[4] Tyrosine can also be obtained through supplementation.

Biosynthesis[link]

Plant biosynthesis of tyrosine from shikimic acid.

In plants and most microorganisms, tyr 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[link]

Catecholamine hormones produced from tyrosine metabolism.

Phosphorylation and sulfation[link]

Some of the tyrosine residues can be tagged with a phosphate group (phosphorylated) by protein kinases. (In its phosphorylated state, it is referred to as 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.^[5] Tyrosine sulfation is catalyzed by tyrosylprotein sulfotransferase (TPST). Like the phosphotyrosine antibodies mentioned above, antibodies have recently been described that specifically detect sulfotyrosine.

Precursor to neurotransmitters and hormones[link]

In dopaminergic cells in the brain, tyrosine is converted to levodopa 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 the catecholamines norepinephrine (noradrenaline) and epinephrine (adrenaline).

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

Precursor to alkaloids[link]

The latex of the 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 .

Also , mescaline producing cactus bio-synthesize tyrosine into mescaline when injected with it .

Precursor to pigments[link]

Tyrosine is also the precursor to the pigment melanin.

Degradation[link]

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.

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-hydroxylphenylpyruvate-dioxygenase and splitting off CO₂ homogentisate (2,5-dihydroxyphenyl-1-acetate). In order to split the aromatic ring of homogentisate, a further dioxygenase, homogentistate-oxygenase is required. Thereby, through the incorporation of a further O₂ molecule, maleylacetoacetate is created.

Fumarylacetate is created 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 via 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.

Betaines[link]

(S)-Tyrosine (left) and (R)-tyrosine (right) in zwitterionic form at neutral pH

Ortho- and meta-tyrosine[link]

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

Three isomers of tyrosine are known. In addition to 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 (m-tyr or 3-hydroxyphenylalanine or L-m-tyrosine) 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.^[6][7]

m-Tyrosine and analogues (rare in nature and therefore available synthetically) have shown application in Parkinson's Disease, Alzheimer's disease and arthritis.^[8]

Medical use[link]

Tyrosine is a precursor to neurotransmitters and increases plasma neurotransmitter levels (particularly dopamine and norepinephrine)^[9] but has little if any effect on mood.^[10][11][12] The effect on mood is more noticeable in humans subjected to stressful conditions (see below).

A number of studies have found tyrosine to be useful during conditions of stress, cold, fatigue,^[13] loss of a loved one such as in death or divorce, prolonged work and sleep deprivation,^[14][15] with reductions in stress hormone levels,^[16] reductions in stress-induced weight loss seen in animal trials,^[13] improvements in cognitive and physical performance^[11][17][18] seen in human trials; however, because tyrosine hydroxylase is the rate-limiting enzyme, effects are less significant than those of l-dopa.

Tyrosine does not seem to have any significant effect on mood, cognitive or physical performance in normal circumstances.^[19][20][21] A daily dosage for a clinical test supported in the literature is about 100 mg/kg for an adult, which amounts to about 6.8 grams at 150 lbs.^[22] The usual dosage amounts to 500–1500 mg per day (dose suggested by most manufacturers; usually an equivalent to 1–3 capsules of pure tyrosine). It is not recommended to exceed 12000 mg (12 g) per day. In fact, too high doses result in reduced levels of dopamine.^[19] Tyrosine may decrease the absorption of other amino acids in high or chronic doses. It decreases absorption of l-dopa.

See also[link]

• Tyramine
• Alkaptonuria
• Tyrosinemia
• Albinism
• Tyrosine sulfation
• Betalain
• Iodinated tyrosine derivatives

References[link]

External links[link]

• Tyrosine metabolism
• Phenylalanine and tyrosine biosynthesis
• Phenylalanine, Tyrosine, and tryptophan biosynthesis
• Tyrosine in the ChemIDplus database