The metabolism of citric acid in the mammary gland. 1. The effect of p-nitrophenol on the synthesis and oxidation of citric acid by homogenates of the mammary gland

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Abstract
Citric acid was oxidized by homogenates of the lactating mammary gland at approximately the same rate as alpha-oxoglutaric acid. Citric acid accumulated in mammary homogenates metabolizing pyruvate or acetate in the presence of fumarate. The amount of citrate accumulating during the metabolism of pyruvate was equal to the difference between the amounts of pyruvate and of added citrate disappearing. It is concluded that the preparation metabolized citrate at a rate corresponding to the overall rate of the citric acid cycle, and that accumulation of citric acid during the metabolism of its precursors was due to an excessive rate of production of "active acetate" and its condensation with oxaloacetate. This observation suggests a simple explanation for the occurrence of citric acid in milk. Addition of p-nitrophenol (2 x 10-4 M) greatly enhanced the respiration of mammary homogenates metabolizing pyruvate plus fumarate, oxaloacetate, citrate and alpha-oxoglutarate, but had much smaller or no stimulating effects in the presence of succinate, fumarate, malate and of acetate plus fumarate. The stimulation of respiration by p-nitrophenol was not accompanied by a corresponding acceleration of substrate disappearance. Phosphate acceptors did not accelerate the respiration unless p-nitrophenol was also added. Mammary homogenates oxidized acetoacetate and octanoate. Fluoride (0.01 M) inhibited the rates of respiration and of substrate disappearance. In the case of certain substrates this inhibition was reversed by the addition of p-nitrophenol.