ON THE UTILIZATION OF ACETIC ACID FOR CHOLESTEROL FORMATION

Abstract

The information at present available as to the metabolism of cholesterol and its relationship to the other biologically important sterols is meager. Balance experiments (1) have demonstrated that cholesterol can be synthesized and destroyed in the animal but have given no convincing evidence as to the nature of specific precursors of cholesterol. In general, balance experiments fail to differentiate between two alternatives, direct utilization of the dietary component or stimulation of a specific process of metabolism. It cannot, for example, be decided whether the increase of cholesterol observed in some experiments after the feeding of fatty substances is the result of conversion of these substances to cholesterol or whether it merely reflects an increased metabolic activity of the organism. An experiment (2) on the rate of formation of cholesterol, carried out with the aid of deuterium, indicated that about half of all the hydrogen atoms of the newly formed cholesterol was derived from the hydrogen of water; the other half must have originated from the carbon-bound hydrogen atoms of some dietary constituent. This evidence eliminated large molecules as immediate precursors, and suggested that “cholesterol . . . is formed by the coupling of smaller molecules, possibly those which have been postulated to be intermediates in the fat and carbohydrate metabolism” (2). The recent observation (3) that the ingestion of deuterio acetic acid, CD&OOH, leads to the formation of deuterio cholesterol supports this view. On the other hand, deuterio cholesterol is not formed after a,& dideuterio propionic acid and deuterio succinic acid are fed. cr,P-Dideuterio butyric acid and 0, y-dideuterio butyric acid were only slightly effective. The deuterium concentrations in the total cholesterol of the experimental animals after the feeding of deuterio acetate for 8 days arc given in Table I. Positive evidence for the utilization of acetate for cholesterol formation was found for mice, growing rats, and adult rats. In each case the concentration of deuterium in the cholesterol was over 3 times that in the body water. The figures in the seventh column give the proportion