Side-chain oxidation of lipoprotein-bound [24,25-3H]cholesterol in the rat: comparison of HDL and LDL and implications for bile acid synthesis.

The purpose of the study was to test the hypothesis that high density lipoprotein (HDL) cholesterol would be more easily oxidized in vivo than low density lipoprotein (LDL) cholesterol. Homologous plasma was incubated with [24,25-3H]cholesterol and fractionated by ultracentrifugation to obtain HDL and LDL each labeled with [3H] free sterol. HDL and LDL labeled with [24,25-3H]cholesteryl esters were prepared by ultracentrifugation of plasma from donor rats injected 24 hr previously with [24,25-3H]cholesterol in propylene glycol. These four labeled lipoproteins were administered to recipient rats. It was found that more tritium oxide (3H2O) was produced after the HDL doses than after the corresponding LDL doses, from 2--3-fold more when lipoprotein free cholesterol was labeled and from 2--6-fold more when lipoprotein cholesteryl esters were labeled. More 3H2O was produced from free cholesterol-labeled lipoproteins than from cholesteryl ester-labeled lipoproteins. Since oxidation of cholesterol is a measure of bile acid formation, it is concluded that under the conditions of the study HDL-cholesterol is a better precursor of bile acids than LDL-cholesterol.