The role of citric acid in the physiology of the prostate: A chromatographic study of citric acid cycle intermediates in benign and malignant prostatic tissue

Abstract

Summary A study of citric acid cycle intermediates in benign and malignant prostatic homogenates was undertaken utilizing a silicic acid column chromatographic technique. The individual organic acids were identified by ascending paper chromatography. In benign prostatic hypertrophy, citrate accumulation was striking. No α-ketoglutaric or succinic acids could be isolated chromatographically in the benign prostatic homogenate. The citrate accumulation may result from the inhibition of isocitric dehydrogenase by excess citrate ions, but, alternatively, it is possible that a primary deficiency of isocitric dehydrogenase exists. In early and advanced prostatic carcinoma there was an equally striking straight line reduction in citrate concentrations directly proportional to the size and extent of the cancer. In advanced carcinoma the citrate values were less than 10 per cent of those found in benign hypertrophy. The phenomenon is believed due to enzymatic deficiencies in the condensation reaction of Ochoa with consequent reduced citrate synthesis. The administration of stilbestrol alone, or combined with castration, depressed the total titrable organic acid and citric acid concentration to the lowest levels recorded in the survey. The total titrable organic acidity and specific citrate concentration of prostatic tissue are reliable indices of the secretory activity of prostatic epithelium. It is apparent from our chromatographic studies that the citric acid cycle may not be normally operative in benign prostatic hypertrophy, in established prostatic carcinoma or in the estrogenized prostate.