View source for Tyrosine

{{NatOrganicBox
| image= [[Image:L-tyrosine-skeletal.png|180px|Skeletal formula of tyrosine]]<br>[[Image:L-tyrosine-3D-sticks.png|160px|3D stick model of tyrosine molecule]]
| name=(''S'')-2-Amino-3-(4-hydroxyphenyl)-propanoic acid
| PubChem = 1153
| CAS = 60-18-4
| SMILES = N[C@@H](Cc1ccc(O)cc1)C(O)=O
| C=9 | H=11 | N=1 | O=3
| mass=181.19 g/mol
}}
{{CMG}}
__NOTOC__


==Overview==

'''Tyrosine''' (abbreviated as '''Tyr''' or '''Y''')<ref>{{cite web | author=IUPAC-IUBMB Joint Commission on Biochemical Nomenclature | title=Nomenclature and Symbolism for Amino Acids and Peptides | work=Recommendations on Organic & Biochemical Nomenclature, Symbols & Terminology
| year = 1983 | url=http://www.chem.qmul.ac.uk/iupac/AminoAcid/ | accessdate=2007-05-17}}</ref> or '''4-hydroxyphenylalanine''', is one of the 20 [[amino acid]]s that are used by [[cell (biology)|cells]] to [[protein biosynthesis|synthesize]] [[protein]]s. This is a [[non-essential amino acid]] and it is found in large quantities in [[casein]]. In fact, the word "tyrosine" is from the [[Greek language|Greek]] ''tyros'', meaning ''cheese'', as it was first discovered in 1846 by German chemist Justus von Liebig in the protein casein from cheese.<ref>[http://www.infoplease.com/ce6/sci/A0849873.html Tyrosine at infoplease.com]</ref><ref>[http://www.etymonline.com/index.php?l=t&p=24 Tyrosine at etymonline.com]</ref>

==Functions==
Aside from being a proteogenic 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 kinase]]s (so-called [[receptor tyrosine kinase]]s).  Phosphorylation of the hydroxyl group changes the activity of the target protein.  

A tyrosine residue also plays an important role in [[photosynthesis]]. In [[chloroplast]]s ([[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 cluster.

==Biosynthesis==
[[Image:Tyrosine biosynthesis2.png|thumb|right|400px|Plant biosynthesis of tyrosine from [[shikimic acid]]. ]]

In plants and most microorganisms, '''tyr''' is produced via [[prephenic acid|prephenate]], an intermediate on the [[shikimic acid|shikimate pathway]].  Prephenate is [[oxidative decarboxylation|oxidatively decarboxylated]] with retention of the [[hydroxyl]] group to give ''p''-hydroxyphenylpyruvate, which is [[transamination|transaminated]] using [[glutamic acid|glutamate]] as the nitrogen source to give tyrosine and [[ketoglutaric acid|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 an hydroxyl group to the end of the 6-carbon aromatic ring of phenylalanine, such that it becomes tyrosine.

==Metabolism==
[[Image:Tyrosine metabolism.png|thumb|right|400px|[[Catecholamine]] [[hormone]]s produced from tyrosine metabolism.]]

===Phosphorylation and sulfation ===
Some of the tyrosine residues can be ''tagged'' with a phosphate group ([[phosphorylation|phosphorylated]]) by [[protein kinase]]s.  (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 [[antibody|antibodies]].  Tyrosine residues may also be modified by the addition of a sulfate group, a process known as [[tyrosine sulfation]].<ref name="pmid17046811">{{cite journal | author = Hoffhines AJ, Damoc E, Bridges KG, Leary JA, Moore KL | title = Detection and purification of tyrosine-sulfated proteins using a novel anti-sulfotyrosine monoclonal antibody | journal = J. Biol. Chem. | volume = 281 | issue = 49 | pages = 37877–87 | year = 2006 | pmid = 17046811 | doi = 10.1074/jbc.M609398200 | issn = }}</ref>  [[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 hormones===
In the [[adrenal gland]], tyrosine is converted to [[levodopa]] by the [[enzyme]] [[tyrosine hydroxylase]] (TH).  TH is also the [[rate-limiting enzyme]] involved in the synthesis of the [[catecholamine]] [[hormone]]s [[dopamine]], [[norepinephrine]] (noradrenaline), and [[epinephrine]].

The [[thyroid]] hormones [[triiodothyronine]] (T<sub>3</sub>) and [[thyroxine]] (T<sub>4</sub>) in the [[colloid]] of the [[thyroid]] also are derived from tyrosine.

===Precursor to alkaloids===
In ''[[Papaver somniferum]]'', the opium poppy, tyrosine is used to produce the [[alkaloid]] [[morphine]].  

===Precursor to pigments===
Tyrosine is also the precursor to the pigment ''[[melanin]]''.

===Degradation===

[[Image:Tyrosinedegradation2.png|thumb|none|700px|The decomposition of tyrosine to [[acetoacetic acid|acetoacetate]] and [[fumarate]].  Two dioxygenases are necessary for the decomposition path.  The end products can then enter into the [[citric acid cycle]]. ]]

<!-- This path is described in Stryer reference -->
The decomposition of L-tyrosine (syn. ''para''-hydroxyphenylalanine) begins with an α-ketoglutarate dependent [[transamination]] through the tyrosine transaminase to ''para''-hydroxyphenyl[[pyruvate]].  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 CO<SUB>2</SUB> [[homogentisic acid|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 O<SUB>2</SUB> 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 [[acetoacetic acid|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]].

==Ortho- and meta-tyrosine==
[[Image:Phe Tyr.png|thumb|right|500px|Enzymatic [[oxidation]] of tyrosine by [[phenylalanine hydroxylase]] (top) and non-enyzmatic oxidation by hydroxyl [[free radical]]s (middle and bottom). ]]

Three [[isomer]]s 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) which 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]].<ref name="pmid16221230">{{cite journal | author = Molnár GA, Wagner Z, Markó L, Kó Szegi T, Mohás M, Kocsis B, Matus Z, Wagner L, Tamaskó M, Mazák I, Laczy B, Nagy J, Wittmann I | title = Urinary ortho-tyrosine excretion in diabetes mellitus and renal failure: evidence for hydroxyl radical production | journal = Kidney Int. | volume = 68 | issue = 5 | pages = 2281–7 | year = 2005 | pmid = 16221230 | doi = 10.1111/j.1523-1755.2005.00687.x | issn = }}</ref><ref name="pmid16298866">{{cite journal | author = Molnár GA, Nemes V, Biró Z, Ludány A, Wagner Z, Wittmann I | title = Accumulation of the hydroxyl free radical markers meta-, ortho-tyrosine and DOPA in cataractous lenses is accompanied by a lower protein and phenylalanine content of the water-soluble phase | journal = Free Radic. Res. | volume = 39 | issue = 12 | pages = 1359–66 | year = 2005 | pmid = 16298866 | doi = 10.1080/10715760500307107 | issn = }}</ref>

m-Tyrosine and analogues (rare in nature and therefore available synthetically) have shown application in [[Parkinson's Disease]], [[Alzheimer's disease]] and [[arthritis]] <ref>''Optimized Synthesis of L-m-Tyrosine Suitable for Chemical Scale-Up'' Cara E. Humphrey, Markus Furegati, Kurt Laumen, Luigi La Vecchia, Thomas Leutert, J. Constanze D. Müller-Hartwieg, and Markus Vögtle Organic Process Research & Development '''2007''', 11, 1069–1075 {{DOI|10.1021/op700093y}}</ref>.

==Medical use==

Tyrosine is a starting material for [[neurotransmitter]]s and increases plasma neurotransmitter levels (particularly dopamine and norepinephrine)<ref name="pmid6885965">{{cite journal | author = Rasmussen DD, Ishizuka B, Quigley ME, Yen SS | title = Effects of tyrosine and tryptophan ingestion on plasma catecholamine and 3,4-dihydroxyphenylacetic acid concentrations | journal = J. Clin. Endocrinol. Metab. | volume = 57 | issue = 4 | pages = 760–3 | year = 1983 | pmid = 6885965 | doi = | issn = }}</ref> but has little if any effect on mood.<ref name="DietMood">{{cite journal |author=Leathwood PD, Pollet P |title=Diet-induced mood changes in normal populations |journal=Journal of psychiatric research |volume=17 |issue=2 |pages=147–54 |year=1982 |pmid=6764931 |doi=}}</ref><ref name="CognBPStress">{{cite journal |author=Deijen JB, Orlebeke JF |title=Effect of tyrosine on cognitive function and blood pressure under stress |journal = Brain Res. Bull. | volume = 33 |issue = 3 |pages = 319–23 |year=1994 | pmid=8293316 | doi=}}</ref><ref name="DietNeur">{{cite journal |author=Lieberman HR, Corkin S, Spring BJ, Wurtman RJ, Growdon JH |title=The effects of dietary neurotransmitter precursors on human behavior. |journal=Am J Clin Nutr. |volume=42 |issue=2 |pages=366-370 |year=1985 |pmid=4025206 }}</ref> 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,<ref name="pmid11267632">{{cite journal | author = Hao S, Avraham Y, Bonne O, Berry EM | title = Separation-induced body weight loss, impairment in alternation behavior, and autonomic tone: effects of tyrosine | journal = Pharmacol. Biochem. Behav. | volume = 68 | issue = 2 | pages = 273–81 | year = 2001 | pmid = 11267632 | doi = 10.1016/S0091-3057(00)00448-2 | issn = }}</ref> prolonged work and sleep deprivation,<ref name="pmid12887140">{{cite journal | author = Magill RA, Waters WF, Bray GA, Volaufova J, Smith SR, Lieberman HR, McNevin N, Ryan DH | title = Effects of tyrosine, phentermine, caffeine D-amphetamine, and placebo on cognitive and motor performance deficits during sleep deprivation | journal = Nutritional Neuroscience | volume = 6 | issue = 4 | pages = 237–46 | year = 2003 | pmid = 12887140 | doi = | issn = }}</ref><ref name="pmid7794222">{{cite journal | author = Neri DF, Wiegmann D, Stanny RR, Shappell SA, McCardie A, McKay DL | title = The effects of tyrosine on cognitive performance during extended wakefulness | journal = Aviation, space, and environmental medicine | volume = 66 | issue = 4 | pages = 313–9 | year = 1995 | pmid = 7794222 | doi = | issn = }}</ref> with reductions in stress hormone levels,<ref name="pmid4068899">{{cite journal |author=Reinstein DK, Lehnert H, Wurtman RJ |title=Dietary tyrosine suppresses the rise in plasma corticosterone following acute stress in rats |journal=Life Sci. |volume=37 |issue=23 |pages=2157–63 |year=1985 |pmid=4068899 |doi=}}</ref> reductions in stress-induced weight loss seen in animal trials,<ref name="pmid11267632">{{cite journal |author=Hao S, Avraham Y, Bonne O, Berry EM |title=Separation-induced body weight loss, impairment in alternation behavior, and autonomic tone: effects of tyrosine |journal=Pharmacol. Biochem. Behav. |volume=68 |issue=2 |pages=273–81 |year=2001 |pmid=11267632 |doi=}}</ref> improvements in cognitive and physical performance<ref name="CognBPStress" /><ref name="Cadets">{{cite journal |author=Deijen JB, Wientjes CJ, Vullinghs HF, Cloin PA, Langefeld JJ |title=Tyrosine improves cognitive performance and reduces blood pressure in cadets after one week of a combat training course |journal=Brain Res. Bull. |volume=48 |issue=2 |pages=203–9 |year=1999 |pmid=10230711 |doi=}}</ref><ref name="MemoryCold">{{cite journal |author=Mahoney CR, Castellani J, Kramer FM, Young A, Lieberman HR |title=Tyrosine supplementation mitigates working memory decrements during cold exposure |journal=Physiology and Behavior |volume=IN PRESS |issue= |pages= |year=2007 |pmid=17585971 |doi=10.1016/j.physbeh.2007.05.003}}</ref> seen in human trials.

Tyrosine does not seem to have any significant effect on mood, cognitive or physical performance in normal circumstances.<ref name="pmid12381742">{{cite journal | author = Chinevere TD, Sawyer RD, Creer AR, Conlee RK, Parcell AC | title = Effects of L-tyrosine and carbohydrate ingestion on endurance exercise performance | journal = J. Appl. Physiol. | volume = 93 | issue = 5 | pages = 1590–7 | year = 2002 | pmid = 12381742 | doi = 10.1152/japplphysiol.00625.2001 | issn = }}</ref><ref name="pmid9623632">{{cite journal | author = Strüder HK, Hollmann W, Platen P, Donike M, Gotzmann A, Weber K | title = Influence of paroxetine, branched-chain amino acids and tyrosine on neuroendocrine system responses and fatigue in humans | journal = Horm. Metab. Res. | volume = 30 | issue = 4 | pages = 188–94 | year = 1998 | pmid = 9623632 | doi = | issn = }}</ref><ref name="pmid10548261">{{cite journal | author = Thomas JR, Lockwood PA, Singh A, Deuster PA | title = Tyrosine improves working memory in a multitasking environment | journal = Pharmacol. Biochem. Behav. | volume = 64 | issue = 3 | pages = 495–500 | year = 1999 | pmid = 10548261 | doi = | issn = }}</ref>

A daily dosage supported in the literature is about 100 mg/kg for an adult. 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.<ref name="pmid12381742">{{cite journal | author = Chinevere TD, Sawyer RD, Creer AR, Conlee RK, Parcell AC | title = Effects of L-tyrosine and carbohydrate ingestion on endurance exercise performance | journal = J. Appl. Physiol. | volume = 93 | issue = 5 | pages = 1590–7 | year = 2002 | pmid = 12381742 | doi = 10.1152/japplphysiol.00625.2001 | issn = }}</ref>

==See also==
* [[Tyramine]]
* [[Alkaptonuria]]
* [[Tyrosinemia]]
* [[Albinism]]
* [[Tyrosine sulfation]]
* [[Betalain]]
* [[:Category:Iodinated_tyrosine_derivatives|Iodinated tyrosine derivatives]]

==References==
{{Reflist|2}}

==External links==
*[http://www.genome.jp/kegg/pathway/map/map00350.html Tyrosine metabolism]
*[http://www.chem.qmul.ac.uk/iubmb/enzyme/reaction/AminoAcid/PheTyr.html Phenylalanine and tyrosine biosynthesis]
*[http://www.genome.jp/kegg/pathway/map/map00400.html Phenylalanine, Tyrosine, and tryptophan biosynthesis]
*[http://www.compchemwiki.org/index.php?title=Tyrosine Computational Chemistry Wiki]

{{AminoAcids}}

[[Category:Proteinogenic amino acids]]
[[Category:Glucogenic amino acids]]
[[Category:Ketogenic amino acids]]
[[Category:Aromatic amino acids]]
[[Category:Phenols]]

[[ar:تيروزين]]
[[ca:Tirosina]]
[[da:Tyrosin]]
[[de:Tyrosin]]
[[es:Tirosina]]
[[eo:Tirozino]]
[[fr:Tyrosine]]
[[ko:티로신]]
[[id:Tirosin]]
[[it:Tirosina]]
[[he:טירוזין]]
[[lv:Tirozīns]]
[[lb:Tyrosin]]
[[lt:Tirozinas]]
[[nl:Tyrosine]]
[[ja:チロシン]]
[[pl:Tyrozyna]]
[[pt:Tirosina]]
[[ru:Тирозин]]
[[su:Tirosin]]
[[fi:Tyrosiini]]
[[sv:Tyrosin]]
[[uk:Тирозин]]
[[zh:酪氨酸]]

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