MULTIPLE BINDING SITES OF HUMAN BRAIN MONOAMINE OXIDASE AS INDICATED BY SUBSTRATE COMPETITION

Abstract—Six endogenous substrates of monoamine oxidase (EC 1.4.3.4) (serotonin,l‐norepinephrine, dopamine, tyramine, tryptamine andβ‐phenethylamine) were used separately and in pairs with human brain mitochondrial extracts. ApparentK1values were obtained from experiments in which only 1 of 2 substrates was isotopically labelled, and these values were compared with experimentalKmvalues.β‐Phenethylamine appears to be metabolized at enzyme active sites independent from those which bind serotonin. The substratel‐norepinephrine competes with serotonin for an enzyme site, but also may be catalysed at an additional site which is independent of serotonin binding. Experiments in which [14C]tryptamine was combined with [3E]serotonin indicated that tryptamine is a much more potent inhibitor of serotonin oxidation than was predicted fromKmvalues. It is suggested that the competition among substrates of MA0 which is observedin uitromay have relevance toin uiuomechanisms for control of biogenic amine concentrations.