Adrenaline oxidative deamination

Ubiquitous mitochondrial monoamine oxidase [monoamine oxygen oxidoreductase (deaminating) (flavin-containing) EC 1.4.3.4 MAO] exists in two forms, namely type A and type B [ monoamine oxidase (MAO) A and B]. They are responsible for oxidative deamination of primary, secondary, and tertiary amines, including neurotransmitters, adrenaline, noradrenaline, dopamine (DA), and serotonin and vasoactive amines, such as tyramine and phenylethylamine. Their nonselec-tive and selective inhibitors ( selective MAO-A and -B inhibitors) are employed for the treatment of depressive illness and Parkinson s disease (PD). 

Although the two major routes for metabolism of adrenaline and noradrenaline are well established, and involve either methylation of the 3-hydroxyl group on the aromatic nucleus or oxidative deamination (cf. refs. 35, 93, 94, 229-231), the evidence to date does not warrant the complete rejection of a further possible metabolic pathway involving oxidation to an aminochrome (such as adrenochrome or noradrenochrome) in some instances. 

The role of amine oxidase in the inactivation of sympathomimetic amines rests on a much firmer basis. The enzymatic oxidative deamination of tyramine was described first by Hare (87). Kohn (105) partially purified it but the enzyme is widely distributed in mammalian tissues (30,109), is cyanide insensitive (15), and has resisted isolation. The name monamine oxidase has been suggested for the enzyme (154) referred to in the literature as tyramine oxidase, adrenaline oxidase (40), and aliphatic amine oxidase (128). 

The major enzymes in catecholamine catabolism are catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). COMT transfers a methyl group from S-adenosyhnethionine (SAM) (Chapter 47) to the oxygen at position 3 of the aromatic ring (Fig. 48.1). The pathway taken is a lottery depending on whether the noradrenaline and adrenaline are first of aU methylated (by COMT) or alternatively oxidatively deaminated (by MAO). If chance determines methylation has priority, then the methylated amines normetadrenaline and metadrenaline are formed prior to the MAO reaction and subsequent oxidation to HMMA (hydroxymethoxyman-... 

The main metabolic pathways for adrenaline and noradrenaline involve two enzyme systems, notably catechol-O-methyltransferase and monoamine oxidase, leading respectively to the formation of 0-methyl derivatives and products in which the ethanolamine side chain of the molecule has undergone oxidative deamination. It has been shown that up to ca. 95 per cent of infused adrenaline and noradrenaline are eliminated in the urine in the form of products resulting from the actions of the enzyme systems described above [254-260]. 

Monoamine oxidases (MAOs) are mitochondrial outer membrane-bound flavoenzymes that catalyze the degradation of biogenic amines, more specifically the oxidative deamination of several important neurotransmitters, including 5-hydroxytiyptamine (5-HT) (or serotonin), histamine, and the catecholamines dopamine, noradrenaline, and adrenaline. There are two isoforms... 

Most mammalian tissues display the presence of MAO-A and MAO-B isoforms with different substrate specificities. For example, MAO-A catalyses the oxidative deamination of serotonin, whereas MAO-B displays higher specificity for benzylamine and P-phenylethylamine. Noradrenaline, adrenaline, tyramine, tryptamine and dopamine are deaminated by both isozymes. In the human brain the hypothalamus and basal ganglia (striatum) show high MAO activity and it has been observed that... 

Biologically the most important metabolic pathway for dopamine is the hydroxylation of its side chain giving noradrenaline. The reaction is catalysed by dopamine-jS-hydroxylase. A -acetylation of dopamine gives N acetyldopamine, 336,i836) powerful inhibitor of dopa-decarboxylase. (768) jV-methylation gives epinine(= A -methyldopamine) which has not so far been shown to occur in man, this may be subsequently hydroxylated in vitro to give adrenaline. Dopamine is deaminated oxidatively to... 

Besides the deamination of side chains, catalysed by amineoxidase, an oxidative degradation of the ring component of certain aromatic amines has been shown in vitro, namely for noradrenaline, adrenaline,... 

---