Studies in cholesterol metabolism in the animal body

1. Experiments are described whose results indicate that the half-life of serum ¹⁴C-labelled cholesterol in the rat was decreased when the animals had been pre-fed a diet containing unsaturated fat. 2. In most of these experiments there was also an indication that the rate of biosynthesis of cholesterol from acetate was increased when the animals had been pre-fed such a diet. 3. A proposed explanation for these phenomena is that unsaturated fatty acids may combine with cholesterol to form esters which are metabolized more readily than are esters formed with other fatty acids. 4. The isolation of a new Lifschútz chromogen is described. The material was present in human serum and leucocytes and in rat serum, skin and liver. It was shown to be identical with the 3ß-oleyl and linoleyl esters of 7α-hydroxycholesterol. 5. The chemical synthesis of a series of 3ß-acyl esters of 7α-hydroxycholesterol is described in detail, as previously a method has been reported only for the acetyl ester. The physical and chromatographic properties of the esters are tabulated. 6. The synthetic esters were used as substrates for enzymic experiments. The results of these experiments show that the cholesterol esterase system of pancreas was effective for both the hydrolysis and synthesis of the esters, and that of liver for hydrolysis only. 7. The esters were efficiently metabolized to bile acids in vitro. 8. Attempts to produce the synthetic esters either by enzymic oxidation or by autoxidatio of cholesteryl esters were not successful. 9. A description is given of the curious changes undergone by the esters on exposure to ultraviolet light. The resultant changes in structure are discussed. 10. A possible Ale for the naturally occurring esters is suggested, whereby they may form an alternative pathway in the production of bile acids from cholesterol. 11. A hypothesis is described in which it is proposed that the preferential oxidation of certain cholesteryl esters to form esters of 7α-hydroxycholesterol may explain the effect of unsaturated fatty acids on cholesterol turnover