Studies on the Relationship Between Glucose Oxidation and Intermediary Metabolism. I. The Influence Of Glycolysis on the Synthesis of Cholesterol and Fatty Acid in Normal Liver12

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Abstract
In order to determine how glucose oxidation influences lipid synthesis, the rate of production of fatty acids and cholesterol was measured in rat liver homogenates during stimulation of the 2 glycolytic pathways[long dash]the Embden-Meyerhof (EM) pathway by addition of diphosphopyridine nucleotide (DPN) and the hexosemonophosphate (HMP) pathway by the addition of triphospho-pyridine nucleotide (TPN). The synthesis of fatty acids and cholesterol was measured by rates of incorporation of acetate-1-C14 into these compounds. Stimulation of the EM pathway by the addition of DPN slightly accelerated fatty acid synthesis and had no effect upon cholesterol production. However, when glycolysis over the HMP pathway was stimulated by addition of TPN to homogenates, a marked increase in fatty acid and cholesterol synthesis was noted. Simultaneous stimulation of both pathways further increased fatty acid synthesis, but depressed cholesterol synthesis relative to that caused by TPN alone. Since glycolysis via either pathway yields energy, but only HMP glycolysis generates TPNH, it seemed likely that this cofactor was responsible for accelerating cholesterol and fatty acid synthesis during HMP glycolysis. This hypothesis was supported by the fact that a different TPNH generating system, TPN plus isocitric dehydrogenase, was capable of substituting for the HMP pathway in enhancing lipid synthesis. It is concluded that the hexosemonophosphate pathway may exert its major function in cellular metabolism, not simply by furnishing energy, but rather by functioning as a TPNH generating system. Since the synthesis of fatty acids and cholesterol is determined in large part by availability of TPNH, the HMP pathway may provide the principal means whereby glycolysis regulates cholesterol and fatty acid metabolism.