Acceleration of Renal Gluconeogenesis by Ketone Bodies and Fatty Acids.

1. Acetoacetate or short-chain fatty acids (acetate, butyrate, propionate, n-hexanoate, n-octanoate) accelerate the rate of glucose formation from lactate, fumarate and other precursors in slices of kidney cortex (rat, rabbit, sheep). The cause of this acceleration has been investigated. 2. There are two different mechanisms of acceleration. At low concentrations of glucogenic precursors the acceleration is mainly due to a ;sparing' action. The substances which accelerate are oxidizable and serve as fuel of respiration in place of the glucogenic precursor. This is indicated by the fact that the ratio lactate used/glucose formed falls in the presence of the accelerators and approaches the value 2. 3. At high concentrations of lactate the acceleration appears to be mainly due to the activation of pyruvate carboxylase by acetyl-coenzyme A. The evidence in support of this is summarized. The results indicate that the activation of pyruvate carboxylase by acyl-coenzyme A discovered by Utter & Keech (1963) in purified enzyme preparations also occurs in crude tissue homogenates and can play a part in the control of oxaloacetate synthesis and gluconeogenesis.