Substrate regulation of monoamine oxidases
The rate of oxidation by monoamine oxidase (MAO) of a particular amine in a given cell depends on the levels of MAO-A and MAO-B expressed in the mitochondrial outer membranes, on the amine concentration and the oxygen concentration. Its disposal will be slowed by the presence of competing amines or endogenous inhibitors. However, substrate binding alters the properties of MAO and influences catalytic turnover. (a) It increases the redox potential of the flavin making possible the transfer of electrons from the higher potential amine. (b) It accelerates the reactivity of the covalently bound flavin with oxygen, effectively increasing the Vm (particularly for MAO-B). (c) It bypasses the generation of free oxidised enzyme in the reaction cycle so that, at high amine concentrations, only the affinity of a substrate or inhibitor for the reduced enzyme (particularly for MAO-A) is important. These changes are induced only by substrate, not by the few stable products available nor by inhibitors suggesting a very specific interaction between a substrate ligand and the enzyme. The altered properties are very different for MAO-A and MAO-B even with the same substrate. Elucidation of the mechanisms involved must await structural information from physical studies, molecular modelling and mutational analysis.
KeywordsMonoamine Oxidase Mitochondrial Outer Membrane Substrate Regulation Free Flavin State Reduction Oxidation
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- McEwen CM Jr, Sasaki G, Lenz WR (1968) Human liver mitochondrial monoamine oxidase. I Kinetic studies of model interactions. J Biol Chem 213: 5217–5225Google Scholar
- Silverman RB (1992) Electron transfer chemistry of monoamine oxidase. Adv Electron Transfer Chem 2: 177–213Google Scholar
- Singer TP (1991) Monoamine oxidases. In: Muller F (ed) Chemistry and biochemistry of flavoenzymes, vol II. CRC Press, Boca Raton, pp 437–470Google Scholar