Biogenic amines, oxidative deamination

The pyrrolizidine nucleus is characteristic of this group of alkaloids. The a is either L-ornithine or L-arginine, and the /3 is a biogenic amine, the putrescine. Oxidative deamination by enzyme NAD+ converts two molecules of putrescine... 

Amine oxidases catalyze the oxidative deamination of both xenobiotic and biogenic amines, and thus have many critical biological functions. Two distinct classes differ in the nature of their prosthetic groups [1]. The flavin-(FAD flavin adenine dinucleotide)-dependent amine oxidases include monoamine oxidases (MAO A and B) and polyamine oxidases. Amine oxidases not containing FAD, the so-called semicarbazide-sensitive amine oxidases (SSAO), include both plasma amine oxidases and tissue amine oxidases. These contain quinonoid structures as redox cofactors that are derived from posttranslationally modified tyrosine or tryptophan side chains, topaoquinone frequently playing this role [2]. 

The biological function of amine oxidases involves the oxidation of biogenic amines formed during normal biological processes. In mammals, the monoamine oxidases are involved in the control of the serotonin catecholamine ratios in the brain, which in turn influence sleep and EEG patterns, body temperature, and mental depression. Two groups of amine oxidases are involved in the oxidative deamination of naturally occurring amines as well as foreign compounds. 

Monoamine oxidases (MAO-A and MAO-B) are mitochondrial enzymes that oxidatively deaminate endogenous biogenic amine neurotransmitters such as dopamine, serotonin, norepinephrine, and epinephrine. MAOs are like EMOs in that they catalyze the oxidation of drugs to produce drug metabolites that are identical in chemical structures to those formed by CYPs. Because the resulting structures are... 

Table IX. Oxidative Deamination of Biogenic Amines by Bulb Mite Homogenates...

Various mechanisms have been studied in relation to the inactivation of monoamines in insects, which include V-acetylation, oxidative deamination, ° 0-sulfate or (S-alanyl conjugation, and sodium-sensitive and sodium-insensitive uptake mechanisms. GC and MS properties were determined for a variety of biogenic amines as their DTFMB-TMS and DTFMB-TBDMS derivatives. Since the first application of HPLC-ED, it has become an increasingly important analytical tool on neuroscience. Recently, microbore HPLC-ED has become the method of choice for the determination of trace biogenic amines and their metabolites. 

Copper amine oxidases (EC 1.4.3.6) [CAOs, amine O2 oxidoreductase (deaminating)] catalyze the oxidative deamination of biogenic amines to corresponding aldehydes and ammonia, accompanied by a two-electron reduction of molecular oxygen to hydrogen peroxide [7] ... 

MAOs are flavin-dependent enzymes that are responsible for the oxidative deamination of biogenic amines by oxidation to the imine followed by nonenzy-matic hydrolysis to afford the corresponding ketone or aldehyde (Scheme 18.9). Upon oxidation of the amine substrate, the reduced flavin cofactor (FADH2)... 

The pyrrolizidine nucleus is characteristic of this group of alkaloids. The a is either L-omithine or l-arginine, and the p is a biogenic amine, the putrescine. Oxidative deamination by the enzyme NAD" converts two molecules of putrescine into the imine (oxidative deamination, Schift-base formation, oxidative reaction again, and the intramolecular Mannich reaction. 

Oxidative Deamination Reactions. The enzymes amine oxidases (AOs) catalyze the oxidative deamination of a wide range of biogenic amines. There are two classes of AOs copper AOs and flavin-containing AOs. Copper-containing AOs catalyze the oxidation of primary amines to aldehydes, with the subsequent release of ammonia and hydrogen peroxide, which requires one copper ion per subunit and topaquinone (TPQ) (2,4,5-trihydroxyphenylalanine) as cofactor (Figure 1.50). 

The latter enzyme, monoamine oxidase (MAO) occurs in two forms A and B and it catalyzes the oxidative deamination of biogenic amines. It is present in the outer mitochondrial membrane. 

The HjOj is a freely diffusible species that can cross membranes. Hence, mitochondria have two major sources of HjO On the one hand, generated by disproportionation of superoxide anion in the mitochondrial membrane and, on the other hand, the oxidative deamination of biogenic amines by the outer mitochondrial membrane-bound monoamine oxidase activity. Mitochondrion-generated is involved in the redox regulation of cell signaling pathways. The steady-state levels of ([HjOJss) determine the cellular redox status and the transition from proliferation to apoptosis and necrosis. 

A summary of amino acid metabolism is given in Figure 19.2. Amino acids are used for protein synthesis and as N and C donors for the synthesis of other types of macromolecule, e.g. the nucleic acids as well as numerous small molecular compounds. After deamination, i.e. removal of the amino group, the carbon skeleton may be used for the formation of glucose or even fats or it may be oxidized to CO2 and water with the production of metabolic energy. Decarboxylation, i.e. removal of the carboxyl group of certain of the amino acids, leads to the production of biogenic amines such as histamine, serotonin and y-aminobutyrate. 

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... 

Monoamine oxidases (MAOs, EC 1.4.3.4) are a family of flavin-dependent metabolic enzymes that catalyze the oxidative deamination of biogenic and xenobi-otic amines. They play an important role in motor and mood control, as well as in the regulation of motivation and other brain functions. Two isoenzymes, MAO-A and -B, are distinguishable on the basis of their in vitro substrate specificity and inhibitor sensitivity [1]. MAO-A has a higher affinity for 5-HT, and to lesser extent, for noradrenaline and dopamine. It is inhibited by low concentrations of clorgyline, whereas MAO-B is more specific toward benzylamine, 2-phenylethylamine, and is inhibited by selegiline (Deprenyl) [2,3]. 

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