Pathways of fatty acid biosynthesis: Conversion of glutamate carbon to fatty acid carbon via citrate by lactating mouse mammary gland and adenocarcinoma of mouse mammary gland

Abstract

1. 1. As a part of a study of fatty acid biosynthesis, we have investigated the utilization of 14C-labeled glutamate, lactate and acetate by slices of lactating mouse mammary gland and adenocarcinoma of mouse mammary gland. 2. 2. It was found that slices of both tissues incorporated 14C-labeled carbon from [2- 14C] and (5- 14C]glutamate, [2- 14C]lactate and [I- 14C]acetate, but not from [I- 14C]-glutamate, into fatty acids. Regardless of the labeled substrate used, its incorporation into fatty acids was significantly higher in the normal tissue. 3. 3. Analyses of the fatty acids synthesized from [5- 14C]glutamate and [I- 14C]-acetate by the normal tissue indicated incorporation entirely via a de novo pathway, giving rise to an average chain length of 10–14 carbons. In the neoplasm, formation of fatty acids from these substrates seems to proceed via the elongation pathway predominantly, giving rise to an average chain length of 16 carbons. 4. 4. The data indicate the operation of a metabolic pathway which permits the conversion of glutamate through α-ketoglutarate, isocitrate, cis-aconitate and citrate to acetyl CoA and oxalacetate in the lactating mouse mammary gland and the mammary adenocarcinoma. The possible significance of this backward pathway in the supply of precursors for fatty acid synthesis is discussed.