Stimulation of dopamine oxidation in liver mitochondria by palmitic acid in the presence of ATP and tert-butylhydroperoxide

The effect of palmitic acid on the oxidation of dopamine, i.e., on the monoamine oxidase (MA-oxidase) activity, was investigated on deenergized liver mitochondria, upon energization by ATP and also in the presence of an oxidizing agent tert-butylhydroperoxide (TBH). It was found that palmitic acid reduces the value of the apparent K _m for dopamine without alteration of the apparent V _max. This points to stimulation of the mitochondrial MA-oxidase activity by palmitic acid at low concentrations of dopamine. Stimulatory effect of palmitic acid may be related to the ability of amphiphilic compounds to increase the negative charge density on the outer mitochondrial membrane. This leads to an increase in the local concentration of positively charged ions of dopamine in the layer adjacent to the membrane near the active site of monoamine oxidase. ATP eliminates the ability of palmitic acid to stimulate the MA-oxidase activity of mitochondria. This effect of ATP is not observed in the presence of the F _O F ₁-ATP-synthase inhibitor oligomycin. Apparently, in the case of vector transport of H⁺ from the matrix induced by ATP-hydrolysis, protonation of palmitic acid anions occurs on the outer mitochondrial membrane, followed by the movement of the neutral molecules to the outer and then to the inner monolayer of the inner membrane. It was found that TBH at a concentration of 300 μM has no significant effect on the ATPase activity of mitochondria and in the presence of ATP and palmitic acid reduces the value of the apparent K _m for dopamine without alteration of the apparent V _max. Antioxidant thiourea eliminates this effect of TBH. We propose that the TBH-induced oxidative stress in the case of ATP-energized mitochondria results in the movement of palmitic acid molecules from the inner to the outer membrane. This leads to an increase in the density of negative charges on the surface of this membrane and, therefore, to the stimulation of the dopamine oxidation.