title: Evidence for the early reduction of the 24,25 double bond in the conversion of lanosterol to cholesterol in cerebrotendinous xanthomatosis.
abstract: The metabolism of lanosterol and 24,25-dihydrolanosterol (DL) was examined in a patient with cerebrotendinous xanthomatosis after intravenous pulse labeling with a mixture of DL-2-14C and 3S,4S,3R,4R-(4-3H)mevalonate. Sterols were isolated from the feces and purified by silver nitrate thin-layer chromatography, and their identities were confirmed by gas-liquid chromatography and mass spectrometry. Their specific activities were then determined and plotted as a function of time. These isotope ratio measurements and specific activity decay curves were consistent with 24,25-dihydrolanosterol and delta7-cholestenol being intermediates in the synthesis of cholesterol from mevalonate and lanosterol, and they suggested that reduction of the lanosterol side chain may occur as an early step in the synthesis of cholesterol. These results are in contrast to the results reported after the administration of triparanol, a delta24-reductase inhibitor.
mesh_terms: D001928:Brain Diseases, Metabolic / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002784:Cholesterol / Q000096:biosynthesis*; D002849:Chromatography, Gas; D002855:Chromatography, Thin Layer; D005243:Feces / Q000032:analysis; D005260:Female; D006801:Humans; D007553:Isotope Labeling; D007810:Lanosterol / Q000378:metabolism*; D013058:Mass Spectrometry; D008875:Middle Aged; D010084:Oxidation-Reduction; D013261:Sterols / Q000378:metabolism; D013710:Tendons; D013997:Time Factors; D014316:Tritium; D014973:Xanthomatosis / Q000378:metabolism*
chemical_list: D002250:Carbon Radioisotopes; D013261:Sterols; D014316:Tritium; D007810:Lanosterol; D002784:Cholesterol