Oxygen dependency of monoamine oxidase activity in the intact lung

Hydrogen peroxide generated by monoamine oxidase (MAO)-mediated deamination of biogenic amines has been implicated in cell signaling and oxidative inj ury. Because the pulmonary endothelium is a site of metabolism of monoamine s present in the venous return, this brings into question a role for MAO in hyperoxic lung injury. The objective of this study was to evaluate the O-2 dependency of the MAO reaction in the lung. To this end, we measured the p ulmonary venous effluent concentrations of the MAO substrate [C-14]phenylet hylamine and its metabolite [C-14] phenylacetic acid after the bolus inject ion of either phenylethylamine or phenylacetic acid into the pulmonary arte ry of perfused rabbit lungs over a range Of Po-2 values from 16 to 518 Torr . The apparent Michaelis constant for O-2 was similar to 18 muM, which is m ore than an order of magnitude less that measured for purified MAO. The res ults suggest a minimal influence of high O-2 on MAO activity in the normal lung and demonstrate the importance of measuring reaction kinetics in the i ntact organ.