The contribution of newly synthesized cholesterol to bile salt synthesis in rats quantified by mass isotopomer distribution analysis
| Autor: | Renze Boverhof, Frans Stellaard, Roel J. Vonk, Folkert Kuipers, Robert H. J. Bandsma, H Elzinga, Gijs T. Nagel, Marc K. Hellerstein, Pieter J. J. Sauer, Richard A. Neese |
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| Přispěvatelé: | Groningen University Institute for Drug Exploration (GUIDE), Center for Liver, Digestive and Metabolic Diseases (CLDM) |
| Jazyk: | angličtina |
| Rok vydání: | 2000 |
| Předmět: |
Male
LIVER Tritiated water Salt (chemistry) Cholesterol 7 alpha-hydroxylase Gas Chromatography-Mass Spectrometry bile salt synthesis Bile Acids and Salts chemistry.chemical_compound Biosynthesis MIDA ACID SYNTHESIS Enterohepatic Circulation stable isotope Animals BIOSYNTHESIS Rats Wistar Chenodeoxycholate Molecular Biology Enterohepatic circulation mass spectrometry chemistry.chemical_classification Chromatography 7-ALPHA-HYDROXYLASE Cholesterol PRECURSOR POOLS cholesterogenesis PLASMA-CHOLESTEROL Reproducibility of Results HUMANS Cell Biology Metabolism TRITIATED-WATER Rats chemistry Biochemistry bile salt TURNOVER |
| Zdroj: | Biochimica et biophysica acta-Molecular and cell biology of lipids, 1483(3), 343-351. ELSEVIER SCIENCE BV |
| ISSN: | 1388-1981 |
| Popis: | A new stable isotope procedure has been developed and validated in rats, applying [1-C-13]acetate infusion to quantify the production of bile salts from de novo synthesized cholesterol making use of the mass isotopomer distribution analysis (MIDA) principle. Ions (m/z) 458-461, 370-373 and 285-288 were monitored by GC/MS (EI-mode) for the methyl trimethylsilylether derivatives of cholate, chenodeoxycholate and beta-muricholate, respectively. Rats with intact exteriorized enterohepatic circulation and rats with chronic bile diversion were infused with [1-C-13]acetate for up to 14 h. After 10 h of infusion the enterohepatic circulation of the intact group was interrupted to deplete the existing bile salt pool (acute bile diversion). The fractions of biliary cholesterol and individual bile salts derived from newly synthesized cholesterol were determined by MIDA at t = 14 h. In rats with acute bile diversion, these fractions were 20, 25, 27 and 23% for biliary cholesterol, cholate, chenodeoxycholate and beta-muricholate, respectively. After bile diversion for 8 days to induce hepatic cholesterol and bile salt synthesis, these fractions increased significantly to 32, 47, 41 and 47%, respectively. Calculated enrichments of the acetyl-CoA precursor pools were similar for all bile salts and biliary cholesterol within the two rat groups. However, chronic enterohepatic interruption decreased the acetyl-CoA pool size almost two-fold. We conclude that MIDA is a validated new stable isotope technique for studying the synthetic pathway from acetyl-CoA to bile salts. This technique provides an important new tool for studying bile salt metabolism in humans using stable isotopes. (C) 2000 Elsevier Science B.V. All rights reserved. |
| Databáze: | OpenAIRE |
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