Unconjugated bile salts

Polydispersity of simple bile salt micelles can only be assessed by modem QLS techniques employing the 2nd cumulant analysis of the time decay of the autocorrelation function [146,161]. These studies have shown, in the cases of the 4 taurine conjugates in 10 g/dl concentrations in both 0.15 M and 0.6 M NaCl, that the distribution in the polydispersity index (V) varies from 20% for small n values to 50% for large n values [6,146]. Others [112] have foimd much smaller V values (2-10%) for the unconjugated bile salts in 5% (w/v) solutions. Recently, the significance of QLS-derived polydispersities have been questioned on the basis of the rapid fluctuation in n of micellar assemblies hence V may not actually represent a micellar size distribution [167-169]. This argument is specious, since a micellar size distribution and fast fluctuations in aggregation number are identical quantities on the QLS time scale (jusec-msec) [94]. 

Fig. 34.11. Conjugation of bile salts. Conjugation lowers the pK of the bile salts, making them better detergents i.e., they are more ionized in the contents of the intestinal lumen (pH = 6) than are the unconjugated bile salts (pK => 6). The reactions are the same for the chenochoMc acid series of bile salts.

A second mode of movement is passive ionic diffusion. In this process, the bile salt anion moves through the membrane barrier driven by electrochemical difference. Anions of both conjugated and unconjugated bile salts are involved in this process. 

When bile salts are deconjugated by abnormal bacterial proliferation in the small bowel (40), yielding free or unconjugated bile salts with a pK of 4-6, they are quickly absorbed by nonionic diffusion in the jejunum so that intraluminal bile salt concentration may be insufficient for efficient fat absorption and steatorrhea may result (41). 

Bile salts have been used for centuries as digestive aids and cathartics. Their use for these purposes has become more limited recently, and this is probably appropriate until better preparations become available and indications for their administration become more clearly defined. Most commercial bile salt preparations are desiccated or crude extracts of cattle bile containing mainly unconjugated bile salts with small amounts of pigment and lipids. They are generally supplied as 0.2- or 0.3-g tablets. The customary dose is 0.4-0.6 g three times daily with meals. This is probably an inadequate dose, as will be explained later. Dehydrocholic acid, 3,7,12-triketo-5j -cholanoic acid, is oxidized cholic acid and is supplied in pure form but does not form micelles and hence probably does not assist fat absorption significantly and would be of little value for replacement therapy. Sodium dehydrocholate is supplied as a 20 % solution in ampules and is widely used to measure blood circulation times. It does not appear to be conjugated by the liver (86). 

Reabsorption of bile acids is very effective, so that only a small percentage escapes into the cecum. The rest returns via the portal circulation as conjugates [or as unconjugated bile salts if free bile acids were present in the gut lumen (34)] into the liver, thus completing the enterohepatic circulation. Before resecretion, free bile salts are conjugated in the liver with taurine and glycine. 

Ninomiya, R., Matsuoka, K., Moroi, Y. Micelle formation of sodium chenodeox-ycholate and solubilization into the micelles comparison with other unconjugated bile salts. Biochim. Biophys Acta 2003, 1634(3), 116-125. 

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