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Tyrosine

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Tyrosine
Skeletal formula of the L-isomer
Ball-and-stick model of the L-isomer as a zwitterion
Names
IUPAC name
(S)-Tyrosine
Other names
L-2-Amino-3-(4-hydroxyphenyl)propanoic acid
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.000.419 Edit this at Wikidata
  • 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
  • N[C@@H](Cc1ccc(O)cc1)C(O)=O
Properties
C9H11NO3
Molar mass 181.191 g·mol−1
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).
☒N verify (what is checkY☒N ?)

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

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

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

Biosynthesis

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

Catecholamine hormones produced from tyrosine metabolism.

Phosphorylation and sulfation

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

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

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

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

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

Ortho- and meta-tyrosine

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

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

References

  1. ^ IUPAC-IUBMB Joint Commission on Biochemical Nomenclature (1983). "Nomenclature and Symbolism for Amino Acids and Peptides". Recommendations on Organic & Biochemical Nomenclature, Symbols & Terminology. Retrieved 2007-05-17.
  2. ^ "Tyrosine". The Columbia Electronic Encyclopedia, 6th ed. Infoplease.com — Columbia University Press. 2007. Retrieved 2008-04-20. {{cite web}}: Cite has empty unknown parameter: |coauthors= (help)
  3. ^ Douglas Harper (2001). "Tyrosine". Online Etymology Dictionary. Retrieved 2008-04-20. {{cite web}}: Cite has empty unknown parameter: |coauthors= (help)
  4. ^ "Tyrosine". University of Maryland Medical Center. Retrieved 2011-03-17.
  5. ^ Hoffhines AJ, Damoc E, Bridges KG, Leary JA, Moore KL (2006). "DETECTION AND PURIFICATION OF TYROSINE-SULFATED PROTEINS USING A NOVEL ANTI-SULFOTYROSINE MONOCLONAL ANTIBODY". J. Biol. Chem. 281 (49): 37877–87. doi:10.1074/jbc.M609398200. PMC 1764208. PMID 17046811.{{cite journal}}: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
  6. ^ 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 (2005). "Urinary ortho-tyrosine excretion in diabetes mellitus and renal failure: evidence for hydroxyl radical production". Kidney Int. 68 (5): 2281–7. doi:10.1111/j.1523-1755.2005.00687.x. PMID 16221230.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  7. ^ Molnár GA, Nemes V, Biró Z, Ludány A, Wagner Z, Wittmann I (2005). "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". Free Radic. Res. 39 (12): 1359–66. doi:10.1080/10715760500307107. PMID 16298866.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  8. ^ 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
  9. ^ Rasmussen DD, Ishizuka B, Quigley ME, Yen SS (1983). "Effects of tyrosine and tryptophan ingestion on plasma catecholamine and 3,4-dihydroxyphenylacetic acid concentrations". J. Clin. Endocrinol. Metab. 57 (4): 760–3. doi:10.1210/jcem-57-4-760. PMID 6885965.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  10. ^ Leathwood PD, Pollet P (1982). "Diet-induced mood changes in normal populations". Journal of Psychiatric Research. 17 (2): 147–54. doi:10.1016/0022-3956(82)90016-4. PMID 6764931.
  11. ^ a b Deijen JB, Orlebeke JF (1994). "Effect of tyrosine on cognitive function and blood pressure under stress". Brain Res. Bull. 33 (3): 319–23. doi:10.1016/0361-9230(94)90200-3. PMID 8293316.
  12. ^ Lieberman HR, Corkin S, Spring BJ, Wurtman RJ, Growdon JH (1985). "The effects of dietary neurotransmitter precursors on human behavior". Am J Clin Nutr. 42 (2): 366–370. PMID 4025206.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  13. ^ a b Hao S, Avraham Y, Bonne O, Berry EM (2001). "Separation-induced body weight loss, impairment in alternation behavior, and autonomic tone: effects of tyrosine". Pharmacol. Biochem. Behav. 68 (2): 273–81. doi:10.1016/S0091-3057(00)00448-2. PMID 11267632.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  14. ^ Magill RA, Waters WF, Bray GA, Volaufova J, Smith SR, Lieberman HR, McNevin N, Ryan DH (2003). "Effects of tyrosine, phentermine, caffeine D-amphetamine, and placebo on cognitive and motor performance deficits during sleep deprivation". Nutritional Neuroscience. 6 (4): 237–46. doi:10.1080/1028415031000120552. PMID 12887140.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  15. ^ Neri DF, Wiegmann D, Stanny RR, Shappell SA, McCardie A, McKay DL (1995). "The effects of tyrosine on cognitive performance during extended wakefulness". Aviation, space, and environmental medicine. 66 (4): 313–9. PMID 7794222.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  16. ^ Reinstein DK, Lehnert H, Wurtman RJ (1985). "Dietary tyrosine suppresses the rise in plasma corticosterone following acute stress in rats". Life Sci. 37 (23): 2157–63. doi:10.1016/0024-3205(85)90566-1. PMID 4068899.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  17. ^ Deijen JB, Wientjes CJ, Vullinghs HF, Cloin PA, Langefeld JJ (1999). "Tyrosine improves cognitive performance and reduces blood pressure in cadets after one week of a combat training course". Brain Res. Bull. 48 (2): 203–9. doi:10.1016/S0361-9230(98)00163-4. PMID 10230711.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  18. ^ Mahoney CR, Castellani J, Kramer FM, Young A, Lieberman HR (2007). "Tyrosine supplementation mitigates working memory decrements during cold exposure". Physiology and Behavior. IN PRESS (4): 575–82. doi:10.1016/j.physbeh.2007.05.003. PMID 17585971.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  19. ^ a b Chinevere TD, Sawyer RD, Creer AR, Conlee RK, Parcell AC (2002). "Effects of L-tyrosine and carbohydrate ingestion on endurance exercise performance". J. Appl. Physiol. 93 (5): 1590–7. doi:10.1152/japplphysiol.00625.2001. PMID 12381742. {{cite journal}}: Unknown parameter |doi_brokendate= ignored (|doi-broken-date= suggested) (help)CS1 maint: multiple names: authors list (link)
  20. ^ Strüder HK, Hollmann W, Platen P, Donike M, Gotzmann A, Weber K (1998). "Influence of paroxetine, branched-chain amino acids and tyrosine on neuroendocrine system responses and fatigue in humans". Horm. Metab. Res. 30 (4): 188–94. doi:10.1055/s-2007-978864. PMID 9623632.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  21. ^ Thomas JR, Lockwood PA, Singh A, Deuster PA (1999). "Tyrosine improves working memory in a multitasking environment". Pharmacol. Biochem. Behav. 64 (3): 495–500. doi:10.1016/S0091-3057(99)00094-5. PMID 10548261.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  22. ^ Gelenberg, A.J., Wojcik, J.D., Growdon, J.H., Sved, A.F., and Wurtman, R.J. "Tyrosine for the Treatment of Depression" (PDF). Archived from the original (PDF) on 2008-06-11. Retrieved 2008-03-25.{{cite web}}: CS1 maint: multiple names: authors list (link)
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