Utilization of acetoacetic acid in cholesterol synthesis by surviving rat liver.

During the course of feeding experiments with nn-phenylalanine, labeled in the ring with deuterium, it was found that the liver and carcass cholesterol of the rats contained deuterium. Further, liver slice studies with ring-labeled phenylalanine showed that the deuterium content of the cholesterol was not proportionately lowered by the presence of large excesses of non-isotopic acetate.’ It has been established by liver perfusion experiments (1) and the liver slice technique (2) that phenylalanine can give rise to acetoacetic acid. Recently Schepartz and Gurin have shown by means of radiocarbon that the methyl and carbonyl carbons of this acetoacetate are derived from the carbon atoms of the benzene ring of phenylalanine (3). It seemed likely therefore that acetoacetic acid was a precursor in the biological synthesis of cholesterol. To study this problem, radiocarbonlabeled acetoacetic acid was synthesized and its conversion to cholesterol studied by means of surviving rat liver.