Pyruvate and Glucose as Precursors of Acetoacetate

Summary

1. The ketogenic power of various C¹⁴-labeled substrates, incubated with actively respiring homogenates of mammary gland and of kidney cortex, has been compared by measuring rate of incorporation of the substrate carbon into carrier-acetoacetate. Whereas acetate and pyruvate were strongly ketogenic, glucose and lactate gave rise to only small amounts of acetoacetate. The analogous behavior of glucose and lactate in contrast with that of pyruvate, indicates that the low ketogenicity of glucose and its ability to stimulate lipogenesis is associated with the regeneration of reduced pyridine nucleotides during its breakdown. 2. No antiketogenic action of glucose was observed when this was added to mammary homogenates metabolizing 1-C¹⁴ acetate. Under certain conditions, the presence of glucose resulted in the acceleration of the appearance of acetate-carbon in respiratory CO₂ and in acetoacetate. This ‘ketogenic’ action appeared to be due to stimulation by glucose of the activation of acetate and consequently the formation of aceto-acetyl-coenzyme A at a rate exceeding the rate of regeneration of reduced pyridine nucleotide coupled with the breakdown of glucose.