Exchange of methyl hydrogens in ethanol during incorporation in bile acids in vivo.
[2,2,2-2H]Ethanol was administered continuously to bile fistula rats for 72 h, with or without (--)-hydroxycitrate. The deuterium labelling of biliary bile acids was determined by GC-MS and 13C NMR. Difference spectra between 2H,1H- and 1H-decoupled 13C NMR spectra showed the presence of partly deuterated methyl and methylene groups in methyl cholate, indicating exchange of deuterium in [2,2,2-2H]ethanol for protium prior to or during incorporation of acetate into the bile acid. The extent of exchange was 20--30% as calculated from the isotopic composition of a fragment ion containing one methyl and one methylene group derived from C-2 of acetate. The exchange was unaffected by (--)-hydroxycitrate, indicating that it was not due to reversible incorporation of deuterated acetate into citrate. About 60% of the acetyl-CoA serving as precursor of cholic and chenodeoxycholic acids were derived from ethanol. This value was not changed by administration of (--)-hydroxycitrate. The half-life time of cholesterol molecules acting as precursors of both bile acids was about 50 h in the presence of (--)-hydroxycitrate, which is about the same as previously found in the absence of the inhibitor.
D000105:Acetyl Coenzyme A / Q000378:metabolism; D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis*; D002793:Cholic Acids / Q000378:metabolism; D002951:Citrates / Q000494:pharmacology*; D000431:Ethanol / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D006859:Hydrogen / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051381:Rats
D001647:Bile Acids and Salts; D002793:Cholic Acids; D002951:Citrates; D000431:Ethanol; D000105:Acetyl Coenzyme A; D006859:Hydrogen; C007999:hydroxycitric acid