KINETIC-PROPERTIES OF CLONED HUMAN LIVER MONOAMINE-OXIDASE-A

Monoamine oxidases deaminate many amines, including neurotransmitters, by oxidation followed by spontaneous breakdown of the imine product. The reduced enzyme is reoxidized slowly by oxygen, but in the presence of amines, the rate of reoxidation is markedly enhanced. The extent o f enhancement depends on the amine substrate, kynuramine enhancing the rate 125-fold, but 5-hydroxytryptamine only 6-fold. Here we describe the properties of human liver monoamine oxidase A which has been clone d into and overexpressed in yeast. The purified enzyme has a higher K- m for oxygen than does the placental enzyme, but the steady-state para meters for the endogenous amines are the same. Tertiary amines are oxi dized at slightly different rates by the two enzymes. The consequences of the branched pathway mechanism with substrate-dependent enhancemen t of reoxidation for the steady-state levels of the various enzyme spe cies is discussed