The reaction of bovine and rat liver monoamine oxidase with [14C]-clorgyline and [14C]-deprenyl
Salach, J.I.; Detmer, K.; Youdim, M.B.
Molecular Pharmacology 16(1): 234-241
1979
ISSN/ISBN: 0026-895X PMID: 481419 Document Number: 151987
Highly purified monoamine oxidase from beef and rat liver was compared with regard to the presence of A and B type enzymes. The beef enzyme oxidizes B and A-B type substrates rapidly and A type substrates slowly in both membrane and soluble preparations. Deprenyl, a selective inhibitor of the B type enzyme, inhibits it at very low concentrations and the I50 is about the same with A, B and A-B type substrates. Clorgyline, a selective inhibitor of the A type enzyme, inhibits only at high concentrations, and the I50 value is again independent of the substrate used. Apparently only the B type enzyme occurs in beef liver. Rat liver contains both A and B types of monoamine oxidase. Deprenyl inhibits the oxidation of B substrates at low concentrations, and clorgyline inhibits oxidation of A substrates at low concentrations, while biphasic inhibition is seen with A-B substrates upon titration with either inhibitor. Deprenyl and pargyline are stoichiometrically bound to the beef and rat liver enzymes, but clorgyline is bound to the beef enzyme in amounts in considerable stoichiometric excess, indicating nonspecific binding. The enzyme from both sources binds the acetylenic suicide inhibitors at N-5 of the covalently bound flavin in a flavocyanine linkage. No conversion of the A to the B type of enzyme on extraction of the enzyme from the membrane and removal of lipids was noted.