Species differences in the selective inhibition of monoamine oxidase (1-methyl-2-phenylethyl)hydrazine and its potentiation by cyanide.
The potentiating effects of cyanide on the inhibition of rat liver mitochondrial monoamine oxidase-A & B and of ox liver mitochondrial MAO-B by pheniprazine [(1-methyl-2-phenylethyl)hydrazine] has been studied. Pheniprazine was shown to behave as a mechanism-based MAO inhibitor. For rat liver MAO-B, the initial non-covalent step was characterized by dissociation constant (K (i)) of 2450 nM and the first-order rate constant (k (+2)) for the covalent adduct formation was 0.16 min(-1). As a reversible inhibitor it was selective towards rat liver MAO-A (K (i) = 420 nM) but the rate of irreversible inhibition of that enzyme was considerably slower (k (+2) = 0.06 min(-1)). MAO-B from ox liver more closely resembled MAO-A from the rat in sensitivity to reversible inhibition by pheniprazine (K (i) = 450 nm) but it was closer to rat liver MAO-B in rate of irreversible inhibition (k (+2) = 0.29 min(-1)). The K (i) values were significantly decreased in the presence of KCN but there was little effect on the k (+2) values. However, sensitivities of the different enzymes to KCN varied widely and considerably higher concentrations of KCN were required for this effect to be apparent with the rat liver mitochondrial MAO-A than with MAO-B from rat and ox liver. The kinetic behaviour of cyanide activation was consistent with partial (non-essential) competitive activation in all cases.
Ramadan
Zakia Ben
ZB
Department of Biochemistry, Trinity College, Dublin, 2, Ireland.
Wrang
Maria L
ML
Tipton
Keith F
KF
D000465:Algorithms; D000818:Animals; D001596:Benzylamines / Q000378:metabolism; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006834:Hydrazines / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010084:Oxidation-Reduction; D011190:Potassium Cyanide / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity
D001596:Benzylamines; D004791:Enzyme Inhibitors; D006834:Hydrazines; D008996:Monoamine Oxidase Inhibitors; C084776:pheniprazine; C030796:benzylamine; D011190:Potassium Cyanide