THE EFFECT OF NEUTRAL SALTS ON PARTICLE PREPARATIONS FROM RAT LIVER: I. THE EFFECT OF NEUTRAL SALT ON PYRUVATE OXIDATION

Abstract

The effect of neutral salts on the utilization of pyruvate by saline-washed particles from rat liver has been investigated in the presence of ATP, Mg++, and fluoride. Addition of increasing quantities of NaCl, KCl, LiCl, or an osmolar equivalent of sucrose to particle preparations metabolizing pyruvate produced a pronounced inhibition of oxygen consumption, which was characterized by a sharp threshold of onset. In the presence of relatively high concentrations of salt, lactate formation is reduced but ketone body synthesis is only slightly impaired. No protection from salt inhibition was afforded by pretreatment of the particles with pyruvate. Fluoride appears to sustain the inhibition produced by the osmotic activity of NaCl. The inhibition is associated with a lack of utilization of pyruvate but produces no change in oxaloacetate levels. The oxidation of D-(−)-β-hydroxybutyrate under these conditions seems to be unimpaired. Within limits, the elevation of the osmolarity appeared to be without effect on oxidative phosphorylation, regardless of the substrate, but was associated with certain well-defined morphological changes in the mitochondrion.