Gülberk UÇAR*,o

*Hacettepe University, Faculty of Pharmacy, Department of Biochemistry, 06100 Sıhhiye, Ankara, TURKEY.
oCorresponding author

Summary:
Monoamine oxidase (MAO), a mitochondrial enzyme which catalyzes the oxidative deamination of major neurotransmitter amines, exists in two forms, designated as MAO-A and B with different substrate specificities and sensitivities to the selective inhibitors. In spite of considerable progress in understanding the interactions of these forms with their preferred substrates,no general rules are yet available for the mechanism of their action towards the specific substrates. This study was planned as a preliminary investigation in order to detect the basic kinetic mechanisms of MAO isoforms towards their subtrates. MAO was purified from rat liver mitochondrial pellets and human platelets.Substrate specificities of the isoforms were investigated by using ptyramine, 5-hydroxytryptamine (serotonin) and benzylamine as substrates.The inhibition kinetics of the isoforms were tested by using the selective inhibitors of MAO-A and B forms such as clorgyline and pargyline.
p-tyramine appeared as a mixed-type substrate since clorgyline or pargyline inhibited both the A and B forms when p-tyramine was used as substrate, suggesting that it would be a preferred nonselective substrate for distinguishing the MAO subtypes.
Benzylamine was found to be a selective substrate particularly for MAO-B isoform purified from human platelets.Pargyline caused a significant inhibition of the MAO-B activity of human platelets when benzylamine was used as substrate.
Serotonin was deaminated mainly by MAO-A and clorgyline inhibited the activity of this form isolated from rat liver homogenates.The present study indicated that the substrate specificities and kinetic behaviors of MAO isoforms might be essential for the design of the new selective MAO inhibitors.