Squalene as a precursor of cholesterol in liver.

Many compounds have been implicated as capable of serving as precursors for cholesterol, and of these the most intriguing is undoubtedly squalene. In 1926, and again in 1937, Channon (1, 2) reported that the .feeding of squalene to rats resulted in an increased cholesterol content of the liver. These observations led Srere (3), in 1949, in this laboratory, to study the conversion of acetate-Cl4 to cholesterol in liver slices prepared from rats fed a diet containing 1 per cent squalene. The livers from the squalene-fed rats showed a marked depression in their incorporation of the Cl4 into cholesterol but not into COz. Since such a depression is compatible with the idea t,hat the fed squalene had diluted a metabolic pool in the path of conversion of acetate to cholesterol, we next undertook the synthesis of CY4-labeled squalene, and this synthesis was reported elsewhere (4). Surprisingly enough, practically no U4-cholesterol was recovered in the liver when the labeled squalene was administered to rats or when the labeled compound was incubated with liver slices in a bicarbonate medium. Langdon and Bloch, however, have reported that the Cl4 of biologically prepared U4-squalene can be incorporated into cholesterol in vivo (5). An explanat.ion of the failure of the synthetic squalene to be incorporated into cholesterol was suggested by examination of the infra-red spectra of the natural and synthetic compounds (6). It was found that the synthetic material, as well as the natural squalene regenerated from the solid hexahydrochloride, di$ered from the naturally occurring material in the types of carbon-carbon double bonds. In the present investigation, we have compared the effects of feeding natural squalene and regenerated squalene upon hepatic cholesterogenesis from added acet,at’e-C14.