Tyrosine metabolism p.1 (dopamine)

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 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) [13], [14], 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 [11], [15].

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].

References:

1. 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
2. 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
3. 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
4. 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
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
6. Frigon RP, Stone RA
   Human plasma dopamine beta-hydroxylase. Purification and properties. The Journal of biological chemistry 1978 Oct 10;253(19):6780-6
7. Kitabchi AE, Williams RH
   Phenylethanolamine-N-methyltransferase in human adrenal gland. Biochimica et biophysica acta 1969 Mar 18;178(1):181-4
8. KIRSHNER N, GOODALL M
   The formation of adrenaline from noradrenaline. Biochimica et biophysica acta 1957 Jun;24(3):658-9
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
10. 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
11. 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
12. Suzuki O, Matsumoto T
    Normetanephrine and metanephrine oxidized by both types of monoamine oxidase. Experientia 1985 May 15;41(5):634-6
13. 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
14. 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
15. 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
16. 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
17. 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
18. 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
19. 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
20. 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