Absence of a Relation between Lipogenesis and Ketogenesis in vivo

Abstract

IN the normal liver acetyl-coenzyme A is formed from glucose, fatty acids and the keto-acids produced by deamination and transamination of amino-acids. It is removed by oxidation, by fatty acid synthesis and, to a small extent, by ketone body formation (Fig. 1). Lipogenesis is defective in the livers of diabetic and fasting animals, a block occurring in the path of conversion of acetyl-coenzyme A to fatty acids¹. Formerly, many workers related the development of ketosis to a diminished rate of oxidation of acetyl-coenzyme A, due to a possible lowering in the level of oxaloacetate. Lately, as a result of experiments in vitro, increased ketogenesis has been attributed to a diversion in the utilization of acetyl-coenzyme A (or acetoacetyl-coenzyme A) from fatty acid synthesis towards the formation of ketone bodies^2–4. Stadie⁴ has advanced the hypothesis that the supply of reduced triphosphopyridine nucleotide, which depends upon the rate of glucose metabolism via the hexosemonophosphate ‘shunt’, regulates fatty acid synthesis and, consequently, ketogenesis.