Pathway Map Details
Tyrosine metabolism p.1 (dopamine)
Object list (links open in MetaCore):
188.8.131.52, 184.108.40.206, 2-(3,4-Dihydroxyphenyl) -acetic acid, COMT, 2-(3,4-Dihydroxyphenyl) -acetaldehyde, Normetanephrine, 220.127.116.11, Vanillylmandelic acid, Levodopa, 18.104.22.168, 22.214.171.124, L-Tyrosine, 126.96.36.199, 188.8.131.52, 184.108.40.206, L-Phenylalanine, (L)-tyrosine*(tRNA), Metanephrine, 220.127.116.11, L-Adrenaline, 18.104.22.168, 22.214.171.124, 126.96.36.199, 188.8.131.52, ABP1, ADHB, MAOB, AOC2, 184.108.40.206, 3-Methoxy-4-hydroxy mandelic aldehyde, PNMT, Dopamine, ADH7, Dopaquinone, 220.127.116.11, 18.104.22.168, 2-(3-Methoxy-4-hydroxy -phenyl)-acetaldehyde, 22.214.171.124, 3,4-Dihydroxy phenylglycol, TY3H, 126.96.36.199, AOC3, L-Noradrenaline, TYRO, PAH, 188.8.131.52, DDC, 184.108.40.206, Homovanillic acid, 220.127.116.11, 18.104.22.168, 2-(3-Methoxy-4-hydroxy- phenyl)-acetaldehyde, 22.214.171.124, DBH, AL1B1, TyrRS, 126.96.36.199, 188.8.131.52, COMT, 184.108.40.206, ALD9A1, 3,4-Dihydroxy mandelic acid, MAOA, 3,4-Dihydroxy mandelaldehyde, 3-Methoxytyramine, AL3A1, 220.127.116.11
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 .
- Martinez A, Knappskog PM, Olafsdottir S, D??skeland AP, Eiken HG, Svebak RM, Bozzini M, Apold J, Flatmark T
Expression of recombinant human phenylalanine hydroxylase as fusion protein in Escherichia coli circumvents proteolytic degradation by host cell proteases. Isolation and characterization of the wild-type enzyme. The Biochemical journal 1995 Mar 1;306 ( Pt 2):589-97
- Jia J, Li B, Jin Y, Wang D
Expression, purification, and characterization of human tyrosyl-tRNA synthetase. Protein expression and purification 2003 Jan;27(1):104-8
- Nasrin S, Ichinose H, Hidaka H, Nagatsu T
Recombinant human tyrosine hydroxylase types 1-4 show regulatory kinetic properties for the natural (6R)-tetrahydrobiopterin cofactor. Journal of biochemistry 1994 Aug;116(2):393-8
- Wittbjer A, Odh G, Rosengren E, Rorsman H
Enzymatic and non-enzymatic oxygenation of tyrosine. Pigment cell research / sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society 1996 Apr;9(2):92-5
- Mappouras DG, Stiakakis J, Fragoulis EG
Purification and characterization of L-dopa decarboxylase from human kidney. Molecular and cellular biochemistry 1990 May 10;94(2):147-56
- Frigon RP, Stone RA
Human plasma dopamine beta-hydroxylase. Purification and properties. The Journal of biological chemistry 1978 Oct 10;253(19):6780-6
- Kitabchi AE, Williams RH
Phenylethanolamine-N-methyltransferase in human adrenal gland. Biochimica et biophysica acta 1969 Mar 18;178(1):181-4
- KIRSHNER N, GOODALL M
The formation of adrenaline from noradrenaline. Biochimica et biophysica acta 1957 Jun;24(3):658-9
- Borchardt R, Cheng CF
Purification and characterization of rat heart and brain catechol methyltransferase. Biochimica et biophysica acta 1978 Jan 12;522(1):49-62
- Sole MJ, Hussain MN
A simple specific radioenzymatic assay for the simultaneous measurement of picogram quantities of norepinephrine, epinephrine, and dopamine and in plasma and tissues. Biochemical medicine 1977 Dec;18(3):301-7
- Bertocci B, Miggiano V, Da Prada M, Dembic Z, Lahm HW, Malherbe P
Human catechol-O-methyltransferase: cloning and expression of the membrane-associated form. Proceedings of the National Academy of Sciences of the United States of America 1991 Feb 15;88(4):1416-20
- Suzuki O, Matsumoto T
Normetanephrine and metanephrine oxidized by both types of monoamine oxidase. Experientia 1985 May 15;41(5):634-6
- Eisenhofer G, Kopin IJ, Goldstein DS
Catecholamine metabolism: a contemporary view with implications for physiology and medicine. Pharmacological reviews 2004 Sep;56(3):331-49
- Youdim MB
In vivo, noradrenaline is a substrate for rat brain monoamine oxidase A and B. British journal of pharmacology 1983 Jun;79(2):477-80
- Levin JA, Wilson SE
The effect of monoamine oxidase and catechol O-methyltransferase inhibitors on the accumulation and metabolism of [l-3H] norepinephrine by the adventitia and media of rabbit aorta. The Journal of pharmacology and experimental therapeutics 1977 Dec;203(3):598-609
- Nielsen M, Braestrup C
A method for the assay of conjugated 3,4-dihydroxyphenylglycol, a major noradrenaline metabolite in the rat brain. Journal of neurochemistry 1976 Nov;27(5):1211-7
- Rivett AJ, Roth JA
Kinetic studies on the O-methylation of dopamine by human brain membrane-bound catechol O-methyltransferase. Biochemistry 1982 Apr 13;21(8):1740-2
- Jiang H, Jiang Q, Liu W, Feng J
Parkin suppresses the expression of monoamine oxidases. The Journal of biological chemistry 2006 Mar 31;281(13):8591-9
- O'Carroll AM, Fowler CJ, Phillips JP, Tobbia I, Tipton KF
The deamination of dopamine by human brain monoamine oxidase. Specificity for the two enzyme forms in seven brain regions. Naunyn-Schmiedeberg's archives of pharmacology 1983 Apr;322(3):198-202
- Gulliver PA, Tipton KF
The purification and properties of pig-liver catechol-O-methyl transferase. European journal of biochemistry / FEBS 1978 Aug 1;88(2):439-44