Monoamine oxidase inhibitors and liver metabolism: Studies with isolated rat hepatocytes

Abstract

Gluconeogenesis from a range of substrates in isolated liver cells from 48 hr starved rats was inhibited by clorgyline, l-deprenyl, pargyline, tranylcypromine, phenelzine and iproniazid. Generally similar results were seen in cells from fed and diabetic rats and in those from starved guinea pigs. These effects were reversed on removal of inhibitor by washing. Ureogenesis from alanine, but not β-oxidation, was also inhibited by similar concentrations of pargyline and tranylcypromine. The cell contents of malate, aspartate, oxoglutarate and phosphoenolpyruvate were decreased 50 per cent by pargyline. ATP was also decreased to a smaller extent. MAOIs‡ increased oxygen uptake in mitochondria incubated with several substrates (state 4), an effect consistent with a degree of uncoupling of respiration and oxidative phosphorylation. These results are discussed in terms of a non-specific interaction with membrane lipids.