Aliphatic amine oxidase

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 enzyme found in the liver will deaminate secondary and tertiary aliphatic amines as well as primary amines, although the latter are the preferred substrates and are deaminated faster. Secondary and tertiary amines are preferentially dealky la ted to primary amines. For aromatic amines, such as benzylamine, electron-withdrawing substituents on the ring will increase the reaction rate. The product of the reaction is an aldehyde (Fig. 4.30). Amines such as amphetamine are not substrates, seemingly due to the presence of a methyl group on the a-carbon atom (Fig. 4.27). Monoamine oxidase is important in the metabolic activation and subsequent toxicity of allylamine (Fig. 4.31), which is highly toxic to the heart. The presence of the amine oxidase in heart tissue allows metabolism to the toxic metabolite, allyl aldehyde (Fig. 4.31). Another example is the metabolism of MPTP to a toxic metabolite by monoamine oxidase in the central nervous system, which is discussed in more detail in chapter 7. 

Major oxidations are aromatic, aliphatic, alicyclic, heterocyclic, N-oxidation, S-oxidation, dealkylation. Other enzymes also catalyze phase 1 reactions microsomal flavin monooxygenases, amine oxidases, peroxidases, and alcohol dehydrogenase. 

Tyramine has appeared to be ordinarily quite rapidly inactivated in the body, possibly by the amine oxidase mechanism that is active on aliphatic and phenylaliphatic amines. However, this should perhaps be reinvestigated in relation to hypertension in man, for Bain (3) apparently found some isoamylamine in the urine in man, and although Lockett (9) was not able to find this compound in her studies, there are indications of some unknown variables being involved. Lockett did find pressor bases in urine that were more active than isoamylamine and on further study a close correspondence between one of the bases and nicotine was established. However, her preparations of male urine which included some tobacco smokers corresponded to but 50 to 70 micrograms of nicotine per liter in physiological pressor activity and those of female nonsmokers urine, to but 17 micrograms of nicotine per liter. 

In plants, aliphatic di- and polyamines have been implicated in many processes including rapid cell division, fruit development, stress response and senescence (Evans and Malmberg, 1989 Galston and Kaur-Sawhney, 1995). Amine oxidases catalyse the eatabolism of biogenic amines and hence could be involved in regulating sueh eellular processes. It is eonve-nient to separate discussion of the roles of the copper-containing idiamine... 

As well as the microsomal enzymes involved in the oxidation of amines, there are a number of other amine oxidase enzymes which have a different subcellular distribution. The most important are the monoamine oxidases and the diamine oxidases. The monoamine oxidases are located in the mitochondria within the cell and are found in the liver and also other organs such as the heart and central nervous system and in vascular tissue. They are a group of flavoprotein enzymes with overlapping substrate specificities. Although primarily of importance in the metabolism of endogenous compounds such as 5-hydroxytryptamine they may be involved in the metabolism of foreign compounds. The enzyme found in the liver will deaminate secondary and tertiary aliphatic amines as well as primary amines, although the latter are the preferred substrates... 

Of the aliphatic and alicyclic amines, the optimal length of the chain should have seven or eight carbon atoms. Any decrease or increase in the number of carbon atoms results in lowering of the intensity of pressor action. Thus isoamylamine or 4-methyl-2-aminooctane is decidedly less active than forthane or clopane. Prolonged duration of action is acquired by the presence of a methyl group adjacent to the nitrogen atom. Such compounds tend to produce tachyphylaxis and inhibit amine oxidase. 

Table 17. Inhibition of human liver mitochondrial monoamine oxidase by various aliphatic amines and alcohols at different pH values [175]...

An amine oxidase has been purified from pea seedlings by Mann and associates (197,198). The purified enzyme catalyzed the oxidation not only of diamines but also of phenylalkylamines, aliphatic monoamines, and of L-lysine. The rates of oxidation for the latter three were less than for the diamines. The oxidation of all compounds was similarly affected by cyanide and semicarbazide. The conclusion reached was that a single enzyme is involved which is less specific than animal diamine oxidase. 

Amine oxidase is widely distributed among vertebrate and invertebrate tissues, and attacks many aliphatic and aromatic amines, including adrenaline and tyramine. It is distinct from histamine oxidase, which oxidises diamines. 

Diamine Oxidases. Diamine oxidases are enzymes that also oxidize amines to aldehydes. The preferred substates are aliphatic diamines in which the chain length is four (putrescine) or five (cadaverine) carbon atoms. Diamines with carbon chains longer than nine will not serve as substrates but can be oxidized by monoamine oxidases. Secondary and tertiary amines are not metabolized. Diamine oxidases are typically soluble pyridoxal phosphate-containing proteins that also contain copper. They have been found in a number of tissues, including liver, intestine, kidney, and placenta. 

Diamine oxidase, a soluble enzyme found in liver and other tissues, is mainly involved in the metabolism of endogenous compounds such as the aliphatic diamine putrescine (figure 1.26). This enzyme, which requires pyridoxal phosphate, does not metabolize secondary or tertiary amines or those with more than nine carbon atoms. The products of the reaction are aldehydes. 

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