Tyrosine

Tyrosine
Systematic name	(S)-2-Amino-3-(4-hydroxy- phenyl)-propanoic acid
Abbreviations	Tyr Y
Chemical formula	C9H11NO3
Molecular mass	181.19 g mol-1
Melting point	343 °C
Density	1.456 g cm-3
Isoelectric point	5.66
pKa	2.24 9.04 10.10
Molar extinction coefficient	1420 M-1 cm-1 at 274.6 nm
PubChem	1153
CAS number	[60-18-4]
EINECS number	200-460-4
SMILES	N[C@@H](Cc1ccc(O)cc1)C(O)=O
Absorption and emission spectrum Absorbance and fluorescence of tyrosine in water/buffer
Disclaimer and references

Tyrosine is one of the 20 amino acids that are used by cells to synthesize proteins. It has a phenol side chain with a hydroxyl group. Upon the location of the hydroxyl group, there are three structural isomers of Tyr, namely para-Tyr (p-Tyr), meta-Tyr (m-Tyr) and ortho-Tyr (o-Tyr). Enzymatically, only the first isomer (p-Tyr) is produced from L-Phe by the Phe-hydroxylase enzyme. The other two isoforms, m-Tyr and o-Tyr can be produced as a consequence of free radical attack on Phe in states with increased oxidative stress.

Phenylalanine is an α-amino acid that is found in many proteins (such as hemoglobin, is essential in the human diet, and normally is readily converted to the amino acid tyrosine in the human body.

In humans, the L-isomer of asparagine, which is the only form that is involved in protein synthesis, is one of the 20 standard amino acids common in animal proteins and required for normal functioning in humans. However, asparagine is considered to be a "non-essential amino acid" since it does not have to be taken in with the diet, but can be synthesized by the human body from other compounds through chemical reactions—in this case, synthesized commony from phenylalanine.

Phenylalanine, tyrosine, and tryptophan are the biggest of the standard amino acids.

The intricate coordination of systems in the human body is seen in the process, catalyzed by enzymes, by which l-phenylalanine is degraded into l-tyrosine, which in turn is converted into L-DOPA, which is further metabolized into other vitally important products: dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline). However, in the advent of the lack of a particular enzyme due to a genetic effect, the harmony is disrupted and the body loses its ability to metabolize phenylalanine, resulting in the serious disorder phenylketonuria.

The non-carbohydrate, non-nutritive artificial sweetener and flavor enhancer aspartame (aspartyl-phenylalanine-1-methyl ester) is synthesized from phenylalanine and the non-essential amino acid aspartic acid. Synthesized only from the L-isomers of these amino acids, the sweet taste of aspartame is unexpected: L-phenylalanine has a bitter taste and L-aspartic acid has a flat taste. The discovery, manufacture, and use of aspartame, which is now found in many products, represents an aspect of human creativity, helping to address the human desire for sweet things in the face of deleterious health consequences traced to use of sugar (sucrose). Human creativity, however, can manifest in both ethical and unethical manners. While production of an artificial sweetener can offer the potential for health benefits, it also is alleged that aspartame can be deleterious to one's health and that its approval involved conflicts of interest and lack of sufficient research.

Phenylalanine's three letter code is Phe, its one letter code is F, its codons are UUU and UUC, and its systematic name is 2-Amino-3-phenylpropanoic acid (IUPAC-IUB 1983).

Tyrosine Tyr Y 2-Amino-3-(4-hydroxyphenyl)- propanoic acid

(from the Greek tyros, meaning cheese, as it was first discovered in 1846 by German chemist Justus von Liebig in cheese), 4-hydroxyphenylalanine, or 2-amino-3(4-hydroxyphenyl)-propanoic acid,

Structure

In biochemistry, the term amino acid is frequently used to refer specifically to alpha amino acids: those amino acids in which the amino and carboxylate groups are attached to the same carbon, the so-called α–carbon (alpha carbon). The general structure of these alpha amino acids is:

     R
     |
 H2N-C-COOH
     |
     H

where R represents a side chain specific to each amino acid.

Most amino acids occur in two possible optical isomers, called D and L. The L amino acids represent the vast majority of amino acids found in proteins. They are called proteinogenic amino acids. As the name "proteinogenic" (literally, protein building) suggests, these amino acid are encoded by the standard genetic code and participate in the process of protein synthesis. In phenylalanine, only the L-stereoisomer is involved in synthesis of mammalian proteins.

Phenylalanine's chemical formula is C₆H₅- CH₂- CH(NH₂)-COOH, or in general form C₉H₁₁NO₂ (IUPAC-IUB 1983).

Like tyrosine and tryptophan, phenylalanine contains a large rigid aromatic group on the side chain. Phenylalanine, tyrosine, and tryptophan—like isoleucine, leucine, and valine—are hydrophobic and tend to orient towards the interior of the folded protein molecule. Phenylalanine is classified as nonpolar because of the hydrophobic nature of the benyl side chain. It is a white, powdery solid.

tyrosine molecule

Tyrosine is converted to levodopa by tyrosine hydroxylase, an enzyme.

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 as 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. Tyrosine sulfation is catalyzed by tyrosylprotein sulfotransferase (TPST). Like the phosphotyrosine antibodies mentioned above, antibodies have recently been described that specifically detect sulfotyrosine. Tyrosine is also precursor to the thyroid hormones thyroxine and triiodothyronine, the pigment melanin, and the biologically-active catecholamines dopamine, norepinephrine and epinephrine.

In Papaver somniferum, the opium poppy, it is used to produce morphine.

Biosynthesis

Tyrosine cannot be completely synthesized by animals, although it can be made by hydroxylation of phenylalanine if the latter is in abundant supply. It is produced by plants and most microorganisms from prephenate, an intermediate on the shikimate pathway.

Prephenate is oxidatively decarboxylated with retention of the hydroxyl group to give p-hydroxyphenylpyruvate. This is transaminated using glutamate as the nitrogen source to give tyrosine and α-ketoglutarate.

Metabolic pathways

Simplified pathway for phenylalanine metabolism

The enzyme phenylalanine hydroxylase normally converts the amino acid phenylalanine into the amino acid tyrosine. If this reaction does not take place, phenylalanine accumulates and tyrosine is deficient. Excessive phenylalanine can be metabolized into phenylketones, which are detected in the urine. These include phenylacetate, [[phenylpyruvate] and phenylethylamine. Detection of phenylketones in the urine is diagnostic.

Phenylalanine is a large, neutral amino acid (LNAA). LNAAs compete for transport across the blood brain barrier (BBB) via the large neutral amino acid transporter (LNAAT). Excessive phenylalanine in the blood saturates the transporter. Thus, excessive levels of phenylalanine significantly decrease the levels of other LNAAs in the brain. But since these amino acids are required for protein and neurotransmitter synthesis, phenylalanine accumulation disrupts brain development in children, leading to mental retardation.

File:PKU Adrenaline.PNG

Biosynthesis of neurotransmitters from tyrosine

Tyrosine hydroxylase

Tyrosine hydroxylase (TH) is the rate-limiting enzyme involved in the synthesis of the catecholamines such as dopamine, norepinephrine and epinephrine.

Medical use

L-Tyrosine is sometimes recommended by practitioners as helpful for weight loss, clinical depression, Parkinson's Disease, and phenylketonuria; however, one study found that it had no impact on endurance exercise performance.

Phenylketonuria

Phenylketonuria (PKU) is an autosomal recessive genetic disorder characterized by a deficiency in the enzyme phenylalanine hydroxylase (PAH). This enzyme is necessary to metabolize the amino acid phenylalanine to the amino acid tyrosine. When PAH is deficient, phenylalanine accumulates and is converted into phenylketones, which are detected in the urine.

Left untreated, this condition can cause problems with brain development, leading to progressive mental retardation and seizures. However, PKU is one of the few genetic diseases that can be controlled by diet. A diet low in phenylalanine and high in tyrosine can bring about a nearly total cure.

Phenylketonuria

The genetic disorder phenylketonuria (PKU) is the inability to metabolize phenylalanine. It is a genetic disorder characterized by a deficiency in the enzyme phenylalanine hydroxylase (PAH), which is necessary to metabolize the phenylalanine to tyrosine. When PAH is deficient, phenylalanine accumulates and is converted into phenylketones, which are detected in the urine. These include phenylacetate, phenylpyruvate, and phenylethylamine (Michals and Matalon 1985). Detection of phenylketones in the urine is diagnostic.

Left untreated, this condition can cause problems with brain development, leading to progressive mental retardation and seizures (see Biological aspects above). However, PKU is one of the few genetic diseases that can be controlled by diet. A diet low in phenylalanine and high in tyrosine can bring about a nearly total cure.

Individuals with this disorder are known as "phenylketonurics." Treatment of PKU includes the elimination of phenylalanine from the diet, and supplementation of the diet with tyrosine. Babies who are diagnosed with PKU must immediately be put on a special milk/formula substitute. Later in life, the diet continues to exclude phenylalanine-containing foods. Women affected by PKU must pay special attention to their diet if they wish to become pregnant, since high levels of phenylalanine in the uterine environment can cause severe malformation and mental retardation in the child. However, women who maintain an appropriate diet can have normal, healthy children. This dietary restriction also applies to pregnant women with hyperphenylalanine (high levels of phenylalanine in blood) because they do not properly metabolize phenylalanine.

If PKU is diagnosed early enough, an affected newborn can grow up with normal brain development, but only by eating a special diet low in phenylalanine for the rest of his or her life. This requires severely restricting or eliminating foods high in phenylalanine, such as breast milk, meat, chicken, fish, nuts, cheese, and other dairy products. Starchy foods such as potatoes, bread, pasta, and corn must be monitored. Many diet foods and diet soft drinks that contain the sweetener aspartame must also be avoided, as aspartame consists of two amino acids: phenylalanine and aspartic acid. Aspartame is found in many sugarless gums, sugarless soft drinks (such as Diet Coke, and Diet Pepsi), some forms of Lipton Tea, and a number of other food products.

References

ISBN links support NWE through referral fees

• Doolittle, R. F. 1989. Redundancies in protein sequences. In G. D. Fasman, ed., Prediction of Protein Structures and the Principles of Protein Conformation. New York: Plenum Press. ISBN 0306431319.
• International Union of Pure and Applied Chemistry and International Union of Biochemistry and Molecular Biology (IUPAC-IUB) Joint Commission on Biochemical Nomenclature. 1983. Nomenclature and symbolism for amino acids and peptides: Recommendations on organic & biochemical nomenclature, symbols & terminology. IUPAC-IUB. Retrieved June 14, 2007.
• Lehninger, A. L., D. L. Nelson, and M. M. Cox. 2000. Lehninger Principles of Biochemistry, 3rd ed. New York: Worth Publishing. ISBN 1572591536.
• Michals, K., and R. Matalon. 1985. Phenylalanine metabolites, attention span and hyperactivity. American Journal of Clinical Nutrition. 42(2): 361-365. PMID 4025205.
• Pietz, J., R. Kreis, A. Rupp, E. Mayatepek, D. Rating, C. Boesch, and H. J. Bremer. 1999. Large neutral amino acids block phenylalanine transport into brain tissue in patients with phenylketonuria. Journal of Clinical Investigation 103: 1169–1178. PMID 10207169.

References

• AJ Hoffhines et al. Journal of Biological Chemistry 281:37877-37887, 2006[1]
• GA Molnar et al. Kidney International 68:2281-2287, 2005 Abstract
• GA Molnar et al. Free Radical Research 39(12):1359-1366, 2005 Abstract

External links

• Phenylalanine and tyrosine biosynthesis
• Computational Chemistry Wiki
• Phosphotyrosine Antibody

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