The effect of fumarate and of p-nitrophenol on the synthesis of fatty acids in homogenates of the mammary gland

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Abstract
The aerobic and anaerobic synthesis of fatty acids in cell-free homogenates of mammary gland was studied. In respiring homogenates no measurable synthesis of fatty acids from (carboxy-C14) acetate or (2-C14) pyruvate was observed in the absence of other added substrates. The addition of fumarate in increasing amounts (0.00125-0.005 [image]) resulted in progressive stimulation of fatty acid synthesis accompanied by a progressive decline in the radioactivity of the respiratory CO2. The addition of glucose resulted in further stimulation of lipogenesis. When (carboxy-Cl4) acetate was metabolized in the presence of fumarate, p-nitrophenol (2 x 10-4 [image]) or fluoride (0.005 [image]) inhibited fatty acid synthesis, O2 consumption and C14O2 production; the effects of the 2 inhibitors were additive. In the presence of additional oxidizable substrates such as glucose or pyruvate, the inhibitory action of p-nitrophenol (2 x 10-4 [image]) was diminished and fatty acid synthesis continued at a measurable rate. This protective action was, however, abolished when the concentration of p-nitrophenol was increased to 4 x 10-4 [image]. The inhibition of fatty acid synthesis by p-nitrophenol was accompanied by inhibition of aerobic phosphorylation. The addition of p-nitrophenol to homogenates metabolizing (2-C14) pyruvate in the presence of fumarate resulted in marked inhibition of lipogenesis, while O2 consumption and C14O2 production were increased. These effects of p-nitrophenol were not modified by fluoride, which caused only slight inhibition of fatty acid synthesis. Arsenate inhibited lipogenesis from acetate and from pyruvate. Under anaerobic conditions, fatty acid synthesis from (carboxy-C14) acetate was demonstrated in mammary homogenates showing rapid glycolysis to which either oxaloacetate or citrate had been added.