Metabolism of the cholestanol precursor cholesta-4,6-dien-3-one in different tissues.
Cerebrotendinous xanthomatosis (CTX) is a lipid storage disease where the basic defect is a lack of the mitochondrial C27-steroid 26-hydroxylase involved in bile acid synthesis (EC 1.14.13.15). Cholestanol and cholesterol accumulate in all tissues. At least part of the accumulation of cholestanol is due to a 7 alpha-dehydroxylation of early bile acid intermediates. Cholesta-4,6-dien-3-one, a proposed intermediate in this pathway, is found in increased concentrations in serum of the patients. This study shows that cholesta-4,6-dien-3-one may be metabolized to 4-cholesten-3-one and cholestanol by liver, adrenals and brain. No conversion was found in intestinal mucosa or in kidneys. The capacity to convert cholesta-4,6-dien-3-one into 4-cholesten-3-one and cholestanol varied in different tissues as well as in different species. The results are discussed in relation to the cholestanol accumulation in CTX.
Buchmann
M S
MS
Institute of Clinical Biochemistry, Rikshospitalet, University of Oslo, Norway.
Björkhem
I
I
Skrede
S
S
D000818:Animals; D002777:Cholestanols / Q000096:biosynthesis*; D002782:Cholestenes / Q000378:metabolism*; D002783:Cholestenones / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D007700:Kinetics; D008861:Microsomes / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium
D002777:Cholestanols; D002782:Cholestenes; D002783:Cholestenones; D014316:Tritium; C030311:4,6-cholestadien-3-one