METABOLISM OF LITHOCHOLIC ACID IN BILE FISTULA PATIENTS*

Abstract

Lithocholic acid 1 is rapidly hydroxylated by the rat liver to /8-muricholic acid (1) and at least two other compounds more hydrophilic than lithocholic acid (2). In man, this acid is sometimes present in small quantities in the bile (3) and feces (4), and it is postulated that it may be formed by 7a dehydroxylation of chenodeoxycholic acid by colon bacteria (5). In order to determine if the human liver changes the lithocholic acid molecule into any other compounds, the labeled acid was given intra-venously to two patients, each having a total ex-ternal biliary fistula. METHODS AND RESULTS Labeled lithocholic acid (3a-hydroxycholanic acid-24-C4) was prepared from the norbromide by nitrile syn-thesis (6). Purity of the labeled acid was established by repeated crystallizations from ethanol, acetone, and acetic acid which yielded specific activities differing by less than 10%. Column chromatography with systems I and II (see Table I) demonstrated homogenous behavior and constant specific activity after admixture of the labeled acid with authentic lithocholic acid on both types of col-umns. Descending paper chromatography using system V showed the labeled acid to have the same movement and color of fluorescence with antimony trichloride (11) as lithocholic acid controls. No impurities were detected. Approximately 12 uc of the authentic labeled acid, specific activity 7.8 X 106 cpm per mg, was dissolved in a small volume of ethanol and slowly inj ected through the tubing of an iv saline drip into patient C.A., and ap-proximately 27,uc of the same acid was similarly given to a second patient, L.R. All bile was collected in ethanol. The final volume of each fraction collected was adjusted to contain 50 % ethanol and stored at 50 C. Information concerning the patients. Patient C.A., a 72-year-old woman, had a carcinoma of the gall bladder.