A Novel Pathway for Biosynthesis of Cholestanol with 7a-Hydroxylated C27-Steroids as Intermediates, and Its Importance for the Accumulation of Cholestanol in Cerebrotendinous Xanthomatosis

A mixture of 7a-3H- and 4-'4C-labeled cholesterol was admin-istered intravenously to rats. Cholestanol with 20-30 % lower ratio between 3H and '4C than in cholesterol could be isolated from different organs. In a healthy human control, cholestanol isolated from feces had a 3H/'4C ratio which was 28 % lower than in administered cholesterol. Cholesterol and coprostanol reisolated in these experiments had the same ratio between 3H and 14C as in the precursor. A previously unknown pathway for formation of cholestanol, involving 7a-hydroxylated inter-mediates, may explain these results. Under normal conditions, this pathway is responsible for at most 30 % of the cholestanol synthesized from cholesterol. Intravenous administration of the 7a-3H- and 4-'4C-labeled cholesterol to a patient with cerebrotendinous xanthomatosi