Boris Tabakoff

Ontogeny of multiple forms of monoamine oxidase in mouse brain.

MAO activities in mouse brain responsible for deamination of serotonin (5-HT) and p-dimethylaminobenzylamine (DAB) were found to follow different postnatal developmental patterns. MAO activity which deaminated 5-HT reached adult levels 15 days after birth. At this age the capacity of brain to deaminate DAB was only 50% of adult levels and did not develop fully until after the 45th postnatal day. Inhibitor studies with Deprenil and clorgyline indicated that the deamination of the two substrates was due to different forms of MAO and that these forms were similar to type A and type B MAO described previously in rat brain.

Inhibition of binding of aldehydes of biogenic amines in tissues

Abstract The binding of aldehydes derived from the biogenic amines (i.e. serotonin, dopamine, tryptamine, etc.) is dependent on the substituents attached to the carbonyl residue, as well as the aldehydic group per se . The hydroxyl group on the aromatic nucleus of “biogenic” aldehydes contributes significantly to the attachment of the moieties to brain tissue. Thus, 5-hydroxyindole and catechol were found to compete selectively with the “biogenic” aldehydes for tissue binding sites. The attachment of the “biogenic” aldehydes to tissue may also be prevented in vitro by various reducing or trapping agents, such as ascorbate, cysteine or glutathione. The possible physiologic significance of aldehyde binding to cellular components is discussed.

Alcohol and Aldehyde Metabolism in Brain

The brain is highly sensitive to the effects of an array of drugs, which includes ethanol and its metabolite, acetaldehyde. Although the problem of alcoholism is an old one, little definitive data has emerged from research on the metabolism of ethanol in the central nervous system (CNS). In contrast, peripheral metabolism is fairly well documented, particularly in the case of liver where the greatest ethanol metabolism takes place. Other peripheral tissues such as kidney (1), intestine, lung (2) and blood (3) have been shown to also metabolize ethanol. In the case of liver the metabolism of ethanol to acetate has been shown to alter many homeostatic mechanisms (for review see 5), and such results would be expected to stimulate a search for a similar phenomenon in the central nervous system (CNS). It is specifically this qualitative effect of ethanol metabolism on the normal equilibrium in the CNS that is important, for the metabolism of ethanol by the brain would not contribute a great deal quantitatively to the overall disposition of ethanol and its metabolites in the mammal.

Biogenic aldehyde metabolism relation to pentose shunt activity in brain.

Abstract Biogenic amines, added to brain homogenates, were demonstrated to stimulate oxidative decarboxylation of glucose isotopically labeled at C-1. This effect was ascribed to the stimulation of the pentose phosphate shunt in brain and was found to depend on the monoamine oxidase (MAO)-catalyzed production of the aldehyde derivatives (biogenic aldehydes) of the biogenic amines. The stimulation produced by the amines and the aldehydes was shown to be inhibited by barbiturates, and the enzymes responsible for the stimulated metabolism of glucose were found to be present in the cytosol. Evidence is presented indicating that the stimulation produced by biogenic aldehydes depends on the oxidation of NADPH to NADP by aldehyde reductase present in brain cytosol. Acid derivatives of the biogenic amines [i.e. 5-hydroxyindoleacetic acid (5-HIAA)]were found to inhibit aldehyde-stimulated metabolism of glucose by the pentose phosphate shunt.

Properties of monoamine oxidase in nerve endings from two bovine brain areas

Abstract Monoamine oxidase activity was localized in various subcellular fractions of bovine thalamus and hypothalamus. The recovery of MAO activity was found to parallel two mitochondrial enzymes and was separable from two marker enzymes for the plasma membrane. The MAO activity was found to be higher in the synaptosomes prepared from the hypothalamus compared to the thalamus. These differences in activities were not found for the two other mitochondrial enzymes. Michaelis constants were determined for serotonin and norepinephrine by several methods, both in whole and sonically disrupted mitochondria. Experiments monitoring the deamination of one substrate for MAO, in the presence of a second substrate, and heat denaturation studies demonstrated the presence of two interacting sites for the metabolism of serotonin and norepinephrine in intact mitochondria. The characteristics of these sites were found to depend on the integrity of the mitochondrial membrane.

Addiction to Barbiturates and Ethanol: Possible Biochemical Mechanisms

The possible interaction between ethanol and the metabolism of biogenic amines in brain tissue has long been an area of concerted research. However, only recently have viable theories emerged which may lead to an understanding of the particular biochemical interaction that might be responsible for the development of a state of addiction to ethanol. Such theories have been nurtured by a recognition of a common pathway of catabolism for the deaminated derivatives of the biogenic amines and acetaldehyde, the initial metabolite of ethanol.