Inhibition of mitochondrial nicotinamide nucleotide transhydrogenase by CoA-thioesters of long-chain fatty acids

Abstract

Palmitoyl-CoA is a potent inhibitor (Ki = 0.15 μM) of the nicotinamide nucleotide transhydrogenase reaction catalyzed by submitochondrial particles. The inhibition is competitive selectively with NADP(H), and affects both the nonenergy-linked and energy-linked transhydrogenase reactions. A similar inhibition is demonstrated with intact mitochondria. CoA, acetyl-CoA and acetoacetyl-CoA are without effect; stearoyl-CoA acts less strongly than palmitoyl-CoA. Some implications of these results for the mechanism of the transhydrogenase reaction and its possible metabolic function are discussed. © 1971.