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Tyrosine metabolism p.1 (dopamine)


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Tyrosine metabolism p.1 (dopamine)

Tyrosine metabolism p.1 (dopamine) .

 (L)-Tyrosine is a non-essential aminoacid that issynthesized in mammals from (L)-Phenylalanine by Phenylalanine hydroxylase (PAH ) [1].

(L)-Tyrosine, as other proteogenic aminoacids, conjugates with correspondingtRNA forming (L)-Tyrosine*(tRNA). This reaction is catalyzed by Tyrosyl-tRNAsynthetase ( TyrRS ) [2].

(L)-Tyrosine is converted to Levodopa by Tyrosine hydroxylase (TY3H ) using tetrahydropteridine as a cofactor [3] or by Tyrosinase(oculocutaneous albinism IA) ( TYRO ) . The conversion mediated byTYRO specifically oxidizes Levodopa to Dopaquinone [4].Levodopa is further decarboxylated to Dopamine by Dopa decarboxylase(aromatic L-amino acid decarboxylase) ( DDC ) [5].

Dopamine is an important hormone and neurotransmitter, oxidized toL-Noradrenaline by Dopamine beta-hydroxylase (dopamine beta-monooxygenase) (DBH ) [6]. Phenylethanolamine N-methyltransferase ( PNMT )converts L-Noradrenaline to L-Adrenaline [7], [8].L-Adrenaline is further methylated to Metanephrine by CatecholO-methyltransferase ( COMT ) [9], [10], [11].Further catabolism of Metanephrine leads to Vanillylmandelic acid formationvia two subsequent oxidations: to 3-Methoxy-4-hydroxymandelic aldehyde, catalyzedby monoamine oxidases MAOA and MAOB [12], [13], andthen to Vanillylmandelic acid, catalyzed by A ldehyde dehydrogenase 3 family,memberA1 ( AL3A1 ).

L-Noradrenaline may also be catabolized to Vanillylmandelic acid. It isoxidized to 3,4-Dihydroxymandelaldehyde by Monoamine oxidase A (MAOA ) andMonoamine oxidase B ( MAOB ) [14], [13], that in turn isoxidized to corresponding 3,4-Dihydroxymandelic acid by Aldehyde dehydrogenase 3family, memberA1 ( AL3A1 ). The last step is methylation step to generateVanillylmandelic acid is catalyzed by COMT [15], [11].

Alcohol dehydrogenases: alcohol dehydrogenase 1B (class I), beta polypeptide (ADHB ) and Alcohol dehydrogenase 7 (class IV), mu or sigma polypeptide (ADH7 ) catalyze the formation of the intermediary glycol of L-Noradrenalinemetabolism, 3,4-Dihydroxyphenylglycol, from the corresponding3,4-Dihydroxymandelaldehyde. The glycol is further methylated by COMT toVanylglycol [11], [16], that degrades toVanillylmandelic acid via 3-Methoxy-4-hydroxyphenylglycolaldehyde.COMT directly methylates L-Noradrenaline to generateNormethanephrine [9], [10], [11], which furthermay be oxidized to 3-Methoxy-4-hydroxyphenylglycolaldehyde by MAOA andMAOB [12], [13].

The catabolism of Dopamine is mediated by two pathways, depending on whetherdopamine is deaminated (by monoamine oxidase) or methylated (by catechol O-methyltransferase). Methylation by COMT leads to formation of3-Methoxytyramine [11], [17]. MAOA and MAOBdeaminates 3-Methoxytyramine to 2-(3-Methoxy-4-hydroxy-phenyl)-acetaldehyde[18], that in turn is oxidized to Homovanillic acid by AL3A1.

Direct oxidative deamination of Dopamine by MAOA and MAOB [19] leads to formation of 2-(3,4-Dihydroxyphenyl)-acetaldehyde, which alsodegrades to Homovanillic acid after AL3A1 -catalyzed oxidation to2-(3,4-Dihydroxyphenyl)-acetic acid, followed by COMT -catalyzedmethylation [20].