Content and distribution of pyridine nucleotides in fatty livers

Abstract

Oxidation of some substrates requiring DPN (glutamate, malate, pyruvate, ketoglutarate) is strongly decreased in fatty livers of rats, obtained either by injection of steatogenic poisons (CCl4, P) or by feeding with a diet deficient of choline. The decrease of oxidative power is particularly strong in mitochondria. Addition to these mitochondria of the supernatant fluid produces stimulation of the oxidative activity. Almost complete restoration of activity is produced both in homogenates and in mitochondria by addition of DPN. The concentration of pyridine nucleotides in fatty livers is strongly decreased. The extent of this decrease is particularly remarkable in mitochondria. A redistribution of pyridine nucleotides, with displacement of these substances from mitochondria into the supernatant fluid, occurs in fatty liver homogenates. The PN/PNH ratio is decreased in fatty livers. Synthesis of DPN in vitro through the Kornberg reaction and destruction of DPN are not modified. Both decrease of oxidation of glutamate and decrease and displacement of DPN occur in the livers of treated animals before the beginning of the accumulation of fat within the cells. The possible causes for the described phenomena and their importance for the pathogenesis of liver steatosis are discussed.