Monoamine oxidase B, also known as MAOB, is an enzyme that in humans is encoded by the MAOB gene. The protein encoded by this gene belongs to the flavin monoamine oxidase family. It is an enzyme located in the outer mitochondrial membrane. It catalyzes the oxidative deamination of biogenic and xenobiotic amines and plays an important role in the catabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. This protein preferentially degrades benzylamine and phenylethylamine. Like MAOA, it also degrades dopamine.
Monoamine oxidases (MAOs) serve a crucial function in the regulation of mood and behavior. Flavin-containing MAOs catalyze the oxidative deamination of both dietary and neuroactive monoamines, generating the byproduct hydrogen peroxide (H2O2). The two MAO isoenzymes, MAO A and MAO B, are both expressed on the outer mitochondrial membrane in a variety of brain and peripheral tissues. Prior to their molecular characterization, the distinction between MAO A and MAO B was defined on the basis of substrate and inhibitor sensitivity. MAO A preferentially catabolizes serotonin (5-HT) and norepinephrine (NE), and MAO B prefers the trace amine phenylethylamine (PEA). Both catabolize dopamine (DA), although with differing substrate specificities depending on the species; notably, DA is mainly degraded by MAO A in the rodent brain, while MAO B plays a substantive role in this process in humans and other primates. Despite differences in substrate specificity, enzymatic actions mediated by these two isoenzymes overlap to some degree, resulting in the degradation of monoamines such as tryptamine and tyramine by both forms. Nonetheless, the two isoenzymes are best distinguished based on pharmacological criteria: MAO A is selectively inhibited by low doses of clorgyline whereas MAO B is blocked by low doses of deprenyl.
MAO A and MAO B are encoded by two independent genes that are closely linked on the X chromosome (Xp11.23), in opposite direction with tail-to-tail orientation, and display identical number of exons and intron–exon organization. These similarities, in conjunction with the fact that the primary amino acid sequences of the two isoenzymes have 70% identity, suggest that MAO A and MAO B arose from a common ancestral gene. Despite these similarities, studies of the transcriptional regulation of MAO A and MAO B indicate that these genes are activated and repressed by different transcription factors, which may account for differences in the expression of these two isoenzymes in brain and peripheral tissues and throughout development and aging. Although they are both expressed to some extent in most peripheral tissues and organs, MAO A is the predominant form in the gut and is prevalent in fibroblasts and placental tissue. MAO B is the only isoform in platelets and lymphocytes. Both forms are found in the liver. In the brain, MAO A is primarily expressed in catecholaminergic neurons, whereas MAO B is expressed in serotonergic and histaminergic neurons and glial cells. The underlying reasons for the apparent mismatch of MAO B in serotonergic neurons, however, remain to be elucidated.
MAO B: Relevance for Brain and Behavior
In contrast to the early appearance of MAO A, most studies in humans and rodents indicate that MAO B activity is very low in embryonic brain and increases gradually from birth to adulthood. In rat brain, MAO B activity was found to be very low in all regions at postnatal day 5 but then increased markedly. In human frontal cortex, MAO B activity is fairly constant during childhood but increases in late adulthood. Age-related increases in MAO B in the nigrostriatal dopaminergic system are of great interest due to the marked degeneration of this region in Parkinson's disease (PD). Enhanced MAO B in this system is believed to increase susceptibility to neurodegeneration through production of H2O2 generated during DA oxidation, which contributes to the formation of reactive oxygen species (ROS), triggering mitochondrial damage and neuronal death.
Indeed, MAO B-selective inhibitors have proven highly efficacious in the therapeutic management of PD. The original rationale for using these inhibitors to treat PD was based on the concept that DA is preferentially degraded by MAO B in the human nigrostriatal dopaminergic system, and enhancing DA levels through blockade of MAO B should compensate for the deficits caused by PD. Studies of the MAO B-selective inhibitor, deprenyl, revealed that the effectiveness of this compound is also related to neuroprotective effects induced by MAO inhibition, namely a reduction in oxidative stress.
Reference:Anna Louise Scott. MONOAMINE OXIDASE DEFICIENCY AND EMOTIONAL REACTIVITY: NEUROCHEMICAL AND DEVELOPMENTAL STUDIES