Effects of cinnabarinic acid on mitochondrial respiration

Abstract

The effects of cinnabarinic acid on the respiration of rat liver and beef heart mitochondria in the presence of various substrates were studied. Cinnabarinic acid inhibits respiration of rat liver mitochondria with α-ketoglutarate, malate, isocitrate, pyruvate and glutamate. Oxidation of succinate and β-hydroxybutyrate is not or only slightly inhibited. α-Ketoglutarate oxidation is most sensitive towards cinnabarinic acid followed by pyruvate, glutamate, malate and isocitrate oxidation. Respiration of beef heart mitoehondria is inhibited in the presence of α-ketoglutarate, glutamate, β-hydroxybutyrate and malate. Cinnabarinic acid also activates the adenosine triphosphatase of intact rat liver mitochondria. Mitochondrial respiration inhibited either by rotenone, amytal or antimycin in the presence of β-hydroxybutrate or glutamate is restored by the addition of cinnabarinic acid. This cinnabarinic acidmediated respiration is sensitive to dicumarol and cyanide. Oxidation of α-ketoglutarate blocked by these inhibitors and oxidation of succinate inhibited by antimycin is not restored. The cinnabarinic acid mediated respiration shows some degree of respiratory control. P O ratios of 0–75 were observed. It is concluded that reducing equivalents are transferred from NADH upon the interaction of menadione reductase to cinnabarinie acid and enter the respiratory chain at the level of cytochrome cc 1.