Transformation of 5α-cholest-7-en-3β-ol to cholesterol and cholestanol in cerebrotendinous xanthomatosis

Abstract

The metabolism of Δ7-cholestenol, cholesterol, and cholestanol was examined in a patient with cerebrotendinous xanthomatosis after intravenous pulse-labeling with a mixture of dl-[2-14C]mevalonate and stereospecific 3S,4S,3R,4R-[4-3H]-mevalonate. Silver nitrate and reversed-phase thin-layer chromatography were used to purify the sterols isolated from the feces, and their identities were confirmed by gas–liquid chromatography–mass spectrometry. The specific activities were determined and plotted as a function of time. Isotope ratio measurements and specific activity decay curves showed that sterol synthesis proceeded in the following sequence: mevalonate, squalene, lanosterol, Δ7-cholestenol, cholesterol, cholestanol. Labeled cholesterol precursors might be advantageously used to measure changes in cholesterol synthesis because they appear to equilibrate rapidly and have very short turnover times.

Keywords

• β-sitosterol
• gas–liquid chromatography
• mass spectrometry
• silver nitrate thin-layer chromatography
• reversed-phase thin-layer chromatography
• two-pool model