Pathway Map Details
Tyrosine metabolism p.1 (dopamine)
Object list (links open in MetaCore):
126.96.36.199, 188.8.131.52, 2-(3,4-Dihydroxyphenyl) -acetic acid, COMT, 2-(3,4-Dihydroxyphenyl) -acetaldehyde, Normetanephrine, 184.108.40.206, Vanillylmandelic acid, Levodopa, 220.127.116.11, 18.104.22.168, L-Tyrosine, 22.214.171.124, 126.96.36.199, 188.8.131.52, L-Phenylalanine, (L)-tyrosine*(tRNA), Metanephrine, 184.108.40.206, L-Adrenaline, 220.127.116.11, 18.104.22.168, 22.214.171.124, 126.96.36.199, ABP1, ADHB, MAOB, AOC2, 188.8.131.52, 3-Methoxy-4-hydroxy mandelic aldehyde, PNMT, Dopamine, ADH7, Dopaquinone, 184.108.40.206, 220.127.116.11, 2-(3-Methoxy-4-hydroxy -phenyl)-acetaldehyde, 18.104.22.168, 3,4-Dihydroxy phenylglycol, TY3H, 22.214.171.124, AOC3, L-Noradrenaline, TYRO, PAH, 126.96.36.199, DDC, 188.8.131.52, Homovanillic acid, 184.108.40.206, 220.127.116.11, 2-(3-Methoxy-4-hydroxy- phenyl)-acetaldehyde, 18.104.22.168, DBH, AL1B1, TyrRS, 22.214.171.124, 126.96.36.199, COMT, 188.8.131.52, ALD9A1, 3,4-Dihydroxy mandelic acid, MAOA, 3,4-Dihydroxy mandelaldehyde, 3-Methoxytyramine, AL3A1, 184.108.40.206
Tyrosine metabolism p.1 (dopamine) .
(L)-Tyrosine is a non-essential aminoacid that is synthesized in mammals from (L)-Phenylalanine by Phenylalanine hydroxylase ( PAH ) .
(L)-Tyrosine, as other proteogenic aminoacids, conjugates with corresponding tRNA forming (L)-Tyrosine*(tRNA). This reaction is catalyzed by Tyrosyl-tRNA synthetase ( TyrRS ) .
(L)-Tyrosine is converted to Levodopa by Tyrosine hydroxylase ( TY3H ) using tetrahydropteridine as a cofactor  or by Tyrosinase (oculocutaneous albinism IA) ( TYRO ) . The conversion mediated by TYRO specifically oxidizes Levodopa to Dopaquinone . Levodopa is further decarboxylated to Dopamine by Dopa decarboxylase (aromatic L-amino acid decarboxylase) ( DDC ) .
Dopamine is an important hormone and neurotransmitter, oxidized to L-Noradrenaline by Dopamine beta-hydroxylase (dopamine beta-monooxygenase) ( DBH ) . Phenylethanolamine N-methyltransferase ( PNMT ) converts L-Noradrenaline to L-Adrenaline , . L-Adrenaline is further methylated to Metanephrine by Catechol O-methyltransferase ( COMT ) , , . 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 , , 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 ) , , 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 , .
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 , , that degrades to Vanillylmandelic acid via 3-Methoxy-4-hydroxyphenylglycolaldehyde. COMT directly methylates L-Noradrenaline to generate Normethanephrine , , , which further may be oxidized to 3-Methoxy-4-hydroxyphenylglycolaldehyde by MAOA and MAOB , .
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 , . MAOA and MAOB deaminates 3-Methoxytyramine to 2-(3-Methoxy-4-hydroxy-phenyl)-acetaldehyde , that in turn is oxidized to Homovanillic acid by AL3A1.
Direct oxidative deamination of Dopamine by MAOA and MAOB  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 .
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