Quantitative importance of the 25-hydroxylation pathway for bile acid biosynthesis in the rat
1988; Lippincott Williams & Wilkins; Volume: 8; Issue: 3 Linguagem: Inglês
10.1002/hep.1840080329
ISSN1527-3350
AutoresWilliam Duane, Ingemar Björkhem, Jan Neal Hamilton, Susan M. Mueller,
Tópico(s)Metabolism and Genetic Disorders
ResumoHepatologyVolume 8, Issue 3 p. 613-618 Original ArticleFree Access Quantitative importance of the 25-hydroxylation pathway for bile acid biosynthesis in the rat William C. Duane M.D., Corresponding Author William C. Duane M.D. Department of Medicine, Veterans Administration Medical Center and University of Minnesota, Minneapolis, Minnesota 55417Veterans Administration Medical Center (111D), 54th Street & 48th Avenue South, Minneapolis, Minnesota 55417===Search for more papers by this authorIngemar Björkhem, Ingemar Björkhem Department of Medicine, Veterans Administration Medical Center and University of Minnesota, Minneapolis, Minnesota 55417 Department of Clinical Chemistry, Karolinska Institute, Huddinge University Hospital, Huddinge, SwedenSearch for more papers by this authorJan Neal Hamilton, Jan Neal Hamilton Department of Medicine, Veterans Administration Medical Center and University of Minnesota, Minneapolis, Minnesota 55417 Department of Clinical Chemistry, Karolinska Institute, Huddinge University Hospital, Huddinge, SwedenSearch for more papers by this authorSusan M. Mueller, Susan M. Mueller Department of Medicine, Veterans Administration Medical Center and University of Minnesota, Minneapolis, Minnesota 55417 Department of Clinical Chemistry, Karolinska Institute, Huddinge University Hospital, Huddinge, SwedenSearch for more papers by this author William C. Duane M.D., Corresponding Author William C. Duane M.D. Department of Medicine, Veterans Administration Medical Center and University of Minnesota, Minneapolis, Minnesota 55417Veterans Administration Medical Center (111D), 54th Street & 48th Avenue South, Minneapolis, Minnesota 55417===Search for more papers by this authorIngemar Björkhem, Ingemar Björkhem Department of Medicine, Veterans Administration Medical Center and University of Minnesota, Minneapolis, Minnesota 55417 Department of Clinical Chemistry, Karolinska Institute, Huddinge University Hospital, Huddinge, SwedenSearch for more papers by this authorJan Neal Hamilton, Jan Neal Hamilton Department of Medicine, Veterans Administration Medical Center and University of Minnesota, Minneapolis, Minnesota 55417 Department of Clinical Chemistry, Karolinska Institute, Huddinge University Hospital, Huddinge, SwedenSearch for more papers by this authorSusan M. Mueller, Susan M. Mueller Department of Medicine, Veterans Administration Medical Center and University of Minnesota, Minneapolis, Minnesota 55417 Department of Clinical Chemistry, Karolinska Institute, Huddinge University Hospital, Huddinge, SwedenSearch for more papers by this author First published: May/June 1988 https://doi.org/10.1002/hep.1840080329Citations: 17AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Abstract During biosynthesis of bile acid, carbons 25–26–27 are removed from the cholesterol side chain. Side-chain oxidation begins either with hydroxylation at the 26-position, in which case the three-carbon fragment is released as propionic acid, or with hydroxylation at the 25-position, in which case the three-carbon fragment is released as acetone. In the present study, we have quantitated the relative importance of these two pathways in vivo by measuring production of [14C]acetone from [14C] -26-cholesterol. Four days after intraperitoneal injection of 20 to 40 μCi [14C]-26-cholesterol and 1 day after beginning a constant intravenous infusion of unlabeled acetone at 25 μmoles per kg per min, 6 male and 2 female Sprague-Dawley rats underwent breath collections. Expired acetone was trapped and purified as the 2,4-dinitrophenylhydrazine derivative. 14CO2 was trapped quantitatively using phenethylamine. Specific activity of breath acetone was multiplied times the acetone infusion rate to calculate production of [14C]acetone. [14C] Acetone production averaged 1.7% of total release of 14C from [14C]-26-cholesterol, estimated by 14CO2 output. The method was validated by showing that [14C] acetone production from [14C]isopropanol averaged 111% of the [14C]isopropanol infusion rate. We conclude that, in the normal rat, the 25-hydroxylation pathway accounts for less than 2% of bile acid synthesis. References 1 Elliott WH, Hyde PM. Metabolic pathways of bile acid synthesis. Am J Med 1971; 51: 568– 579. 2 Björkhem I, Gustafsson J, Johansson G, et al. Biosynthesis of bile acids in man: hydroxylation of the C27-steroid side chain. J Clin Invest 1975; 55: 478– 486. 3 Shefer S, Cheng FW, Dayal B, et al. A 25-hydroxylation pathway of cholic acid biosynthesis in man and rat. J Clin Invest 1976; 57: 897– 903. 4 Hanson RF, Staples AB, Williams GC. Metabolism of 5β-cholestane-3α,7α,12α,26-tetrol and 5β-cholestane-3α,7α,12α,25-tetrol into cholic acid in normal human subjects. J Lipid Res 1979; 20: 489– 493. 5 Hanson RF, Williams GC. Metabolism of 3α,7α,12α-trihydroxy-5β-cholestan-26-oic acid in normal subjects with an intact enterohepatic circulation. J Lipid Res 1977; 656– 658. 6 Salen G, Batta AK, Tint GS, et al. The transformation of 3α,7α,12α-trihydroxycoprostanoic acid to cholic acid in humans. In: G Paumgartner, A Stiehl, W Gerok, eds. Bile acids and cholesterol in health and disease: Falk Symposium 33. Boston, Massachusetts: MTP Press Limited, 1983: 91– 98. 7 Shefer S, Dayal B, Tint GS. et al. Identification of pentahydroxy bile alcohols in cerebrotendinous xanthomatosis: characterization of 5β-cholestane-3α,7α,12α,24,25-pentol and 5β-cholestane-3α,7α,12α,23,25-pentol. J Lipid Res 1975; 16: 280– 286. 8 Salen G, Grundy SM. The metabolism of cholestanol, cholesterol, and bile acids in cerebrotendinous xanthomatosis. J Clin Invest 1973; 52: 2822– 2835. 9 Oftebro H, Björkhem I, Skrede S. et al. Cerebrotendinous xanthomatosis: a defect in mitochondrial 26-hydroxylation required for normal biosynthesis of cholic acid. J Clin Invest 1980; 65: 1418– 1430. 10 Salen G, Shefer S, Cheng FW. et al. Cholic acid biosynthesis: the enzymatic defect in cerebrotendinous xanthomatosis. J Clin Invest 1979; 63: 38– 44. 11 Staple E. Mechanism of cleavage of the cholestane side chain in bile acid formation. In: L Schiff, JB Carey, J Dietschy, eds. Bile salt metabolism. Springfield, Illinois: Charles C Thomas, 1969: 127– 139. 12 Danielsson H. Mechanisms of bile acid biosynthesis. In: PP Nair, D Kritchevsky, eds. The bile acids: chemistry, physiology, and metabolism. Vol. 2. Physiology and metabolism. New York: Plenum Press, 1973: 1– 32. 13 Duane WC, Gilberstadt ML, Wiegand DM. Diurnal rhythms of bile acid production in the rat. Am J Physiol 1979; 236: R175– R179. 14 Duane WC, Levitt DG, Mueller SM. Regulation of bile acid synthesis in man: presence of a diurnal rhythm. J Clin Invest 1983; 72: 1930– 1936. 15 Lacouture PG, Wason S, Abrams A. et al. Acute isopropyl alcohol intoxication: diagnosis and management. Am J Med 1983; 75: 680– 686. 16 Williams RT. Detoxication mechanisms: the metabolism and detoxication of drugs, toxic substances and other organic compounds. London, England: Chapman and Hall, 1959. 17 Reichard GA, Haff AC, Skutches CL, et al. Plasma acetone metabolism in the fasting human. J Clin Invest 1979; 63: 619– 626. 18 Mourkides GA, Hobbs DC, Koeppe RE. The metabolism of acetone-2-C14 by intact rats. J Biol Chem 1959; 234: 27– 30. 19 Hillman RE. Simple, rapid method for determination of propionic acid and other short-chain fatty acids in serum. Clin Chem 1978; 24: 800– 803. 20 Kase BF, Pedersen JI, Strandvik B, et al. In vivo and in vitro studies on formation of bile acids in patients with Zellweger's syndrome. J Clin Invest 1985; 76: 2393– 2402. Citing Literature Volume8, Issue3May/June 1988Pages 613-618 ReferencesRelatedInformation
Referência(s)