After oral administration of [2,4-(3)H]-cholyl[(35)S]taurine to eight healthy subjects with indwelling nasoduodenal tubes, the specific activity of the cholyl and taurine moieties and the distribution of radioactivity in biliary bile acid and urinary metabolites, as well as total urinary and fecal (35)S and (3)H, were measured at intervals for 4-8 days. Similar measurements were made after [(35)S]taurine was given orally or intravenously or instilled into the distal intestine. The daily fractional turnover rate of the taurine moiety of cholyltaurine was low and similar to that of the cholyl moiety, indicating that deconjugation occurring during enterohepatic cycling was less than half that previously observed for glycine-conjugated bile acids. Some of the cholyl moiety was absorbed but, since reconjugation occurred predominantly with glycine, little reincorporation into the cholyltaurine pool was observed. Some of the taurine moiety was also absorbed intact but entered large taurine pools, and little reincorporation into the cholyltaurine pool was seen. Oral administration of taurine expanded the cholyltaurine pool and induced a decrease in the fractional turnover rate of the cholyl moiety of cholyltaurine, interpreted to indicate a greater reincorporation of the cholyl moiety because of increased reconjugation with taurine. Taurine moiety not absorbed as taurine appeared to be absorbed largely as sulfate which, like taurine, entered large endogenous pools. Little fecal excretion of (35)S occurred. (35)S was excreted in urine as taurine and sulfate, and excretion in the first 24 h (as percentage of administered dose) correlated highly (r = 0.93) with the daily fractional turnover rate of the taurine moiety. When taurine was instilled into the distal intestine, it appeared as such in plasma, but the more distal the site of instillation, the greater the fraction of urinary (35)S present as sulfate. The [(35)S]sulfate appeared to have come from bacterial degradation of [(35)S]taurine because, when [(35)S]taurine was given intravenously, (35)S was excreted in urine chiefly as [(35)S]taurine with little SO(4)=(-)[(35)S] being present.

Bile↗

PubMed1973

Triketocholanoic (dehydrocholic) acid. Hepatic metabolism and effect on bile flow and biliary lipid secretion in man.

[24-(14)C]Dehydrocholic acid (triketo-5-beta-cholanoic acid) was synthesized from [24-(14)C]cholic acid, mixed with 200 mg of carrier, and administered intravenously to two patients with indwelling T tubes designed to permit bile sampling without interruption of the enterohepatic circulation. More than 80% of infused radioactivity was excreted rapidly in bile as glycine- and taurine-conjugated bile acids. Radioactive products were identified, after deconjugation, as partially or completely reduced derivatives of dehydrocholic acid. By mass spectrometry, as well as chromatography, the major metabolite (about 70%) was a dihydroxy monoketo bile acid (3alpha,7alpha-dihydroxy-12-keto-5beta-cholanoic acid); a second metabolite (about 20%) was a monohydroxy diketo acid (3alpha-hydroxy-7,12-di-keto-5beta-cholanoic acid); and about 10% of radioactivity was present as cholic acid. Reduction appeared to have been sequential (3 position, then 7 position, and then 12 position) and stereospecific (only alpha epimers were recovered). Bile flow, expressed as the ratio of bile flow to bile acid excretion, was increased after dehydrocholic acid administration. It was speculated that the hydroxy keto metabolites are hydrocholeretics. The proportion of cholesterol to lecithin and bile acids did not change significantly after dehydrocholic acid administration. In vitro studies showed that the hydroxy keto metabolites dispersed lecithin poorly compared to cholate; however, mixtures of cholate and either metabolite had dispersant properties similar to those of cholate alone, provided the ratio of metabolite to cholate remained below a value characteristic for each metabolite. These experiments disclose a new metabolic pathway in man, provide further insight into the hydrocholeresis induced by keto bile acids, and indicate the striking change in pharmacologic and physical properties caused by replacement of hydroxyl by a keto substituent in the bile acid molecule.

Bile↗

PubMed1973

Effect of glycine-conjugated bile acids with and without lecithin on water and glucose absorption in perfused human jejunum.

Perfusion studies were performed in healthy volunteers to test whether the secretory effect of conjugated bile acids, previously shown for the colon, was also present in the jejunum. A perfusion system with a proximal occlusive balloon (and continuous aspiration of duodenal secretions) was used; isotonic test solutions contained glycine-conjugated bile acids with or without lecithin. Fluid movement was measured by changes in the concentration of polyethylene glycol (PEG, mol wt 4,000). Conjugated dihydroxy bile acids inhibited electrolyte and fluid absorption and, at higher concentrations, evoked secretion of an isotonic fluid. Glucose absorption continued, despite fluid secretion, but its rate decreased. The secretory effects of bile acids were abolished by the addition of lecithin to the bile acid solutions. A trihydroxy bile acid (cholylglycine) had no effect on jejunal absorption. Small amounts (6-9%) of conjugated bile acids were absorbed in the jejunum; lecithin was well absorbed (72-90%). The results indicate that dihydroxy bile acids influence salt and water transport in the human jejunum but that this effect may be abolished when a polar lipid such as lecithin is present. We speculate that this effect of bile acids may modify fluid movement in the small intestine postprandially after fat absorption has occurred.

Bile Acids and Salts↗