Pathway Map Details

Tyrosine metabolism p.1 (dopamine)

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Object list (links open in MetaCore):,, 2-(3,4-Dihydroxyphenyl) -acetic acid, COMT, 2-(3,4-Dihydroxyphenyl) -acetaldehyde, Normetanephrine,, Vanillylmandelic acid, Levodopa,,, L-Tyrosine,,,, L-Phenylalanine, (L)-tyrosine*(tRNA), Metanephrine,, L-Adrenaline,,,,, ABP1, ADHB, MAOB, AOC2,, 3-Methoxy-4-hydroxy mandelic aldehyde, PNMT, Dopamine, ADH7, Dopaquinone,,, 2-(3-Methoxy-4-hydroxy -phenyl)-acetaldehyde,, 3,4-Dihydroxy phenylglycol, TY3H,, AOC3, L-Noradrenaline, TYRO, PAH,, DDC,, Homovanillic acid,,, 2-(3-Methoxy-4-hydroxy- phenyl)-acetaldehyde,, DBH, AL1B1, TyrRS,,, COMT,, ALD9A1, 3,4-Dihydroxy mandelic acid, MAOA, 3,4-Dihydroxy mandelaldehyde, 3-Methoxytyramine, AL3A1,


Tyrosine metabolism p.1 (dopamine) .

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

(L)-Tyrosine, as other proteogenic aminoacids, conjugates with corresponding tRNA forming (L)-Tyrosine*(tRNA). This reaction is catalyzed by Tyrosyl-tRNA synthetase ( 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 by TYRO 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 to L-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 Catechol O-methyltransferase ( COMT ) [9], [10], [11]. Further catabolism of Metanephrine leads to Vanillylmandelic acid formation via two subsequent oxidations: to 3-Methoxy-4-hydroxymandelic aldehyde, catalyzed by monoamine oxidases MAOA and MAOB [12], [13], and then to Vanillylmandelic acid, catalyzed by A ldehyde dehydrogenase 3 family, memberA1 ( AL3A1 ).

L-Noradrenaline may also be catabolized to Vanillylmandelic acid. It is oxidized to 3,4-Dihydroxymandelaldehyde by Monoamine oxidase A (MAOA ) and Monoamine oxidase B ( MAOB ) [14], [13], that in turn is oxidized to corresponding 3,4-Dihydroxymandelic acid by Aldehyde dehydrogenase 3 family, memberA1 ( AL3A1 ). The last step is methylation step to generate Vanillylmandelic 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-Noradrenaline metabolism, 3,4-Dihydroxyphenylglycol, from the corresponding 3,4-Dihydroxymandelaldehyde. The glycol is further methylated by COMT to Vanylglycol [11], [16], that degrades to Vanillylmandelic acid via 3-Methoxy-4-hydroxyphenylglycolaldehyde. COMT directly methylates L-Noradrenaline to generate Normethanephrine [9], [10], [11], which further may be oxidized to 3-Methoxy-4-hydroxyphenylglycolaldehyde by MAOA and MAOB [12], [13].

The catabolism of Dopamine is mediated by two pathways, depending on whether dopamine is deaminated (by monoamine oxidase) or methylated (by catechol O -methyltransferase). Methylation by COMT leads to formation of 3-Methoxytyramine [11], [17]. MAOA and MAOB deaminates 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 also degrades to Homovanillic acid after AL3A1 -catalyzed oxidation to 2-(3,4-Dihydroxyphenyl)-acetic acid, followed by COMT -catalyzed methylation [20].


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