Hydroxyindole-O-methyltransferase

Fig. 5 Tryptophrin is converted to 5-hydroxytryptophan by tryptophan hydroxylase (1). The production of serotonin in the next step is catalysed by 5-HTP decaiboxylase (a PLP-dependent enzyme). Serotonin is then acetylated to N-acetyl-serotonin by N-acetyltransferase (2). Melatonin is then produced via the action of hydroxyindole-O-methyltransferase (3)...

Hydroxyindole-O-methyltransferase, which is O-methyiates N-acetyiserotonin, serotonin, and other hydroxyindoies, is found in the pineai giand and is invoived in the formation of meiatonin. This enzyme differs from COMT in that it does not methyiate catechoiamines and has no requirement for magnesium iron. 

Serotonin, or 5-HT, is biosynthesized (3) from its dietary precursor L-tryptophan (Fig. 14.1). Serotonergic neurons contain tryptophan hydroxylase (L-tryptophan-5-monooxygenase) that converts tryptophan to 5-hydroxytryptophan (5-HTP) in what is the rate-limiting step in 5-HT biosynthesis and aromatic L-amino acid decarboxylase (previously called 5-HTP decarboxylase) that decarboxylates 5-HTP to 5-HT. This latter enzyme also is responsible for the conversion of L-DOPA to dopamine (see Chapter 12). The major route of metabolism for 5-HT is oxidative deamination by monoamine oxidase (MAO-A) to the unstable 5-hydroxyindole-3-acetaldehyde, which is either reduced to 5-hydroxytryptophol ( 15%) or oxidized to 5-hydroxyindole-3-acetic acid ( -85%). In the pineal gland, 5-HT is acetylated by 5-HT N-acetyltransferase to N-acetylserotonin, which undergoes O-methylation by 5-hydroxyindole-O-methyltransferase to melatonin. 

Tyramine methyltransferase from barley roots Norbelladine-O-mediyltransferase from amarylis bulbs ImidazoIe-N-methyltransferase from guinea pig brain (2.1.1.8) Hydroxyindole-O-methyltransferase from pineal (2.1.1.4) Homocysteine-S-methyltransferase from yeast (2.1.1.10 ) S-Adenosylmethionine cyclotransfeiase from yeast (2.5.1.4) S-Adenosylmethionine decarboxylase from E. coli... 

The oxidation of tryptophan yields serotine, decarboxylation gives tryptamine, the oxidation of which leads to the hormone sero-tonine, from serotonine arises N-acetylserotonine (by the action of N-acetyltransferase), which is the precursor of hormone melatonin, which arises by the action of hydroxyindol-O-methyltransferase (Figure 10.18). An overview of biogenic amines occurring in foods, their preciusors, biological activities and the main products of their transformation is shown in Table 10.22. 

Itoh, M.T. Hattori, A. Sumi, Y. Hydroxyindole-O-methyltransferase activity assay using high-performance liquid chromatography with fluorometric detection determination of melatonin enzymaticsilly formed from iV-acetylserotonin and S-adenosyl-L-methionine, J.Chromatogr.B, 1997, 692, 217-221. 

List of Abbreviations Ach, acetylcholine AMPA, a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid CNS, central nervous system COMT, catechol-O-methyltransferase DA, dopamine DRP-2, dihy-dropyrimidinase-related protein 2 DSM, diagnostic and statistical manual of mental disorders GNAS1, guanine nucleotide-binding protein (G-protein) alpha stimulating activity polypeptide 1 5-HIAA, 5-hydroxyindole acetic acid 5-FIT, serotonin (5-hydroxytryptamine) MAO, monoamine oxidase MHPG, 3-methoxy-4-hydroxyphenylglycol NE, norepinephrine NMDA, N-methyl-D-aspartate PCP, phencyclidine SSRI, selective serotonin reuptake inhibitor SDS, schedule for the deficit syndrome... 

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