Vitamin tyrosine hydroxylase

The first step is catalysed by the tetrahydrobiopterin-dependent enzyme tyrosine hydroxylase (tyrosine 3-monooxygenase), which is regulated by end-product feedback is the rate controlling step in this pathway. A second hydroxylation reaction, that of dopamine to noradrenaline (norepinephrine) (dopamine [3 oxygenase) requires ascorbate (vitamin C). The final reaction is the conversion of noradrenaline (norepinephrine) to adrenaline (epinephrine). This is a methylation step catalysed by phenylethanolamine-jV-methyl transferase (PNMT) in which S-adenosylmethionine (SAM) acts as the methyl group donor. Contrast this with catechol-O-methyl transferase (COMT) which takes part in catecholamine degradation (Section 4.6). 

Monoamine oxidase, tyrosine hydroxylase, and L-amino acid oxidase generate hydrogen peroxide as their reaction product. Hydrogen peroxide is also produced by auto-oxidation of catecholamines in the presence of vitamin C. Moreover, phospholipase A2 (PLA2), cyclooxygenase (COX), and lipoxygenase (LOX), the enzymes associated with arachidonic acid release and the arachidonic acid cascade,... 

Tyrosine is converted to dopa by the rate-limiting enzyme tyrosine hydroxylase, which requires tetrahydrobiopterin, and is inhibited by a-methyltyrosine. Dopa is decarboxylated to dopamine by L-aromatic amino acid decarboxylase, which requires pyridoxal phosphate (vitamin B6) as a coenzyme. Carbidopa, which is used with levodopa in the treatment of parkinsonism, inhibits this enzyme. Dopamine is converted to norepinephrine by dopamine P-hydroxylase, which requires ascorbic acid (vitamin C), and is inhibited by diethyldithiocarbamate. Norepinephrine is converted to epinephrine by phenylethanolamine A -methyltransferase (PNMT), requiring S-adeno-sylmethionine. The activity of PNMT is stimulated by corticosteroids. 

Halasz N, Hokfelt T, Norman AW, Goldstein M. 1985. Tyrosine hydroxylase and 28K vitamin D-dependent calcium binding protein are localized in different subpopulations of periglomerular cells of the rat olfactory bulb. Neurosci Lett 61 103-107. 

Neurons that secrete norepinephrine synthesize it from dopamine in a hydroxylation reaction catalyzed by dopamine (3-hydroxylase (DBH). This enzyme is present only within the storage vesicles of these cells. Like tyrosine hydroxylase, it is a mixed-function oxidase that requires an electron donor. Ascorbic acid (vitamin C) serves as the electron donor and is oxidized in the reaction. Copper (Cu ) is a bound cofactor required for the electron transfer. 

Tetrahydrobiopterin is not a vitamin, because it can be synthesized from GTP, as shown in Figure 10.2 (Thony et al., 2000). It is the coenzyme for mixed-function oxidases phenylalanine, tyrosine, and tryptophan hydroxylases alkyl glycerol monoxygenase, which catalyzes the cleavage of alkyl glycerol ethers and nitric oxide synthase in the formation of nitric oxide. In addition to its coenzyme role, tetrahydrobiopterin has a direct effect on neurons, acting to stimulate dopamine release via a cAMP-dependent protein kinase and a calcium channel (Koshimura et al., 2000). 

C-8) (C-10) Tyrosinemia. There are enzyme defects at steps in the metabolism of tyrosine. These result in the accumulation of tyrosine and its metabolites in the urine and serum. Liver and kidney dysfunction, and mental retardation are common. The condition may be treated by lowering tyrosine and phenylalanine intake. Vitamin C may be helpful as it is a cofactor for hydroxyphenylpy-ruvate hydroxylase at this step. 

Tyrosine monooxygenase uses biopterin as a cofactor. Biopterin is made in the body and is not a vitamin. Its structure resembles that of folic acid. Dopa decarboxylase is a vitamin B -requiring enzyme. Dopamine hydroxylase is a copper metalloenzyme. The active form of the enzyme contains copper in the reduced state (cuprous, Cu+). With each catalytic event, the copper is oxidized to the cupric state (Cu ). The enzyme uses ascorbic acid as a cofactor for converting the cupric copper back to cuprous copper. Thus, each catalytic event also results in the conversion of ascorbic acid to semidehydroascorbate. The semidehydroascorbate, perhaps by disproportionation, is converted to ascorbate and dehydroascorbate. The catalytic cycle of dopamine hydroxylase is shown in Figure 9,86. Dopamine hydroxylase, as well as the stored catecholamines, are located in special vesicles... 

Japanese publications report that vitamin E can be used elfectively in the treatment of facial pigmentation. It inhibits tyrosinase indirectly by inhibiting its hydroxylase activity. It also acts by limiting the oxidative phases required in the first stages of the transformation of tyrosine into indole derivatives. Vitamin E oxidizes easily, and more stable derivatives than pure a-tocopherol have to be used in cosmetic preparations. Tocopheryl acetate is one of the more stable derivatives of vitamin E. Tocopheryl ferulate is also frequently used. 

E. The correct response is very low levels of phoiylalanine hydroxylase, a key oizyme in the metabolic sequelae of phenylketonuria, that is, elevated phenylalanine, phoiylpyruvale, and para-hydroxyphenylpyruvate in blood. Homogentisic acid is an intermediate in the breakdown of tyrosine to fumarate and acetoacetate. Vitamin is required in the metabolism of branched-chain amino acids not phenylalanine. The a-keto acids of the branched chain amino acids produce the maple-syrup odor. 

Tyrosine is the precursor for the synthesis of the hormone and neurotransmitter noradrenalin which is formed from dopamine (3,4-dihydroxyphenylethanolamine) by the vitamin C-requiring dopamine j8-mono-oxygenase (also called dopamine-jS-hydroxylase) in the adrenal medulla as shown in Figure 5.14. 

Phenylalanine is hydroxylated to form tyrosine by a mixed function oxidase, phenylalanine hydroxylase (PAH), which requires molecular oxygen and tetrahy-drobiopterin (Fig. 39.18). The cofactor tetrahydrobiopterin is converted to quininoid dihydrobiopterin by this reaction. Tetrahydrobiopterin is not synthesized from a vitamin it can be synthesized in the body from GTP. However, as is the case with other cofactors, the body contains limited amounts. Therefore, dihydrobiopterin must be reconverted to tetrahydrobiopterin for the reaction to continue to produce tyrosine. 

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