Tyrosine metabolism p.1
(L)-Tyrosine is a non-essential
aminoacid that is synthesized in mammals from
(L)-Phenylalanine by Phenylalanine hydroxylase
(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 Aldehyde 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
COMT directly methylates
L-Noradrenaline to generate
Normethanephrine , , , which further may be oxidized to
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
2-(3-Methoxy-4-hydroxy-phenyl)-acetaldehyde , that in turn is oxidized to Homovanillic acid by
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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