The catalytic behaviour of monoamine oxidase
Evidence concerning the kinetic mechanism of the reaction catalyzed by monoamine oxidase is reviewed with particular reference to the possibility that the double-displacement mechanism followed by other substrates is not operative with benzylamine. The requirement for only one of the two products of the first half-reaction to be released in a double-displacement mechanism indicates that the available evidence does not exclude such a mechanism with benzylamine as the substrate.
Cases in which substrates also act as time-dependent inhibitors are considered. The mechanism that can describe the inhibition and product formation is similar for the compounds MD 780236 and MPTP whereas that describing the effects of high concentrations of 2-phenethylamine is best described by a scheme involving inhibition occuring via an abortive complex.
KeywordsMonoamine Oxidase Kinetic Mechanism Amine Oxidase Amine Substrate Product Inhibition Study
Unable to display preview. Download preview PDF.
- Fersht AR (1977) Enzyme structure and mechanism. Freeman, Reading, pp91, 125–133, 244–273Google Scholar
- Mantle TJ, Tipton KF (1982) Monoamine oxidase A and B: Time for re-evaluation? In: Kalsner S (ed) Trends in autonomic pharmacology, vol 2. Urban & Schwarzenberg, Baltimore, pp 523–542Google Scholar
- Parkinson D, Callingham BA (1980) The binding of [3H]-pargyline to rat liver mitochondrial monoamine oxidase. J Pharm Pharmacol 32: 49– 54Google Scholar
- Roth JA (1979) Effect of drugs on inhibition of oxidized and reduced form of MAO. In: Singer TP, Von Korff RW, Murphy DL (eds) Monoamine oxidase: structure function and altered functions. Academic Press, New York, pp 153–168Google Scholar
- Singer TP (1979) Active-site directed irreversible inhibitors of monoamine oxidase. In: Singer TP, Von Korff RW, Murphy DL (eds) Monoamine oxidase: structure, function and altered functions. Academic Press, New York, pp 7–24Google Scholar
- Singer TP, Salach JI (1981) Interaction of suicide inhibitors with the active site of monoamine oxidase. In: Youdim MBH, Paykel ES (eds) Monoamine oxidase inhibitors–the state of the art. J Wiley, Chichester, pp 17–29Google Scholar
- Tipton KF (1975) Monoamine oxidase. Handbook Physiol Endocrinol 6: 677–697Google Scholar
- Tipton KF, Fowler CJ, McCrodden JM, Strolin Benedetti M (1983) The enzyme-activated irreversible inhibition of type-B monoamine oxidase by 3-(4-[(3 chlorophenyl)methoxy]phenyl)-5-[(methylamino) methyl]-2-oxazolidinone methanesulphate (compound MD 780236) and the enzyme-catalyzed oxidation of this compound as competing reactions. Biochem J 209: 235–242PubMedGoogle Scholar