Bile acid structure and bile formation: a comparison of hydroxy and keto bile acids

The effect of four bile acids, taurocholic (TC), taurochenodeoxycholic (TCDC), tauro-3 alpha,7 alpha-dihydroxy-12-keto-5 beta-cholanoic (T12K), and cholic (C), on bile lipid and water secretion was studied in the bile fistula cat over a 20-fold range of bile acid secretion rates. The critical micellar concentration (CMC) and lecithin-solubilizing capacity of TC, TCDC, and T12K were measured in vitro. T12K and C produced a greater choleresis than TC or TCDC; phospholipid secretion was strikingly reduced with T12K; and cholesterol secretion strikingly increased with TCDC, with a high cholesterol-phospholipid ratio. The estimated CMCs of TC, TCDC, and T12K were 3.3, 0.7, and 6.2 mM respectively; the relative lecithin-solubilizing capacities were 4.4:2.6:1. We conclude that the micellar characteristics of the bile acids studied do not explain the differences in water and lipid secretion observed, and that effects within the hepatocyte may be equally important.