Pathways of fatty acid biosynthesis: Effect of glucose and insulin on the conversion of glutamate carbon to fatty acid carbon via citrate by prelactating tissues and hyperplastic alveolar nodule outgrowths

Abstract

1. 1. The utilization of 14C-labeled glutamate, lactate and acetate by specimens of prelactating tissue taken from pregnant mice and hyperplastic alveolar nodule outgrowths from C 3H mice was investigated. 2. 2. Specimens of both tissues incorporated into fatty acids 14C-labeled carbon from [2- 14C]lactate, [1- 14C] acetate, [2- 14C]glutamate, and [5- 14C]glutamate, but not from [1- 14C]glutamate. Glucose significantly increased the incorporation of these substrates into fatty acids. Insulin stimulated the formation of 14C-labeled fatty acids above levels observed when glucose alone was present. 3. 3. Analyses of the fatty acids synthesized from [5- 14C]glutamate and [1- 14C]-acetate by tissue specimens of the prelactating tissue and the hyperplastic alveolar nodule outgrowths showed that most of the 14C-labeled fatty acids formed were of an average chain length of 16 carbons. In both tissues, formation of fatty acids seems to have proceeded via a mixed mode of synthesis, i.e. the de novo and elongation pathways. 4. 4. The present experiments indicate the operation of an alternate route of glutamate catabolism through α-ketoglutarate, isocitrate, and citrate to acetyl-CoA and oxaloacetate in tissue specimens of the prelactating tissue and the hyperplastic alveolar nodule outgrowths. The possible role of glutamate as an acetyl carrier for fatty acid synthesis in these and other tissues is discussed.