Cholic acid unconjugated

The final passive mechanism is nonionic diffusion. In this case, the solute diffuses as the undissociated acid through the cell membranes, which act as lipid barriers. Concentration difference of the undissociated acid is the driving force. The extent of this process is determined by three factors. The first two, pH of the medium and pKa of the bile acid, define the proportion of molecules in the undissociated state. The third factor, solubility in the lipid membrane, determines the ease of penetration. Taurocholic acid, by virtue of its poor solubility in lipid-like phases and its very low pKa, does not participate significantly in this process. On the other hand, unconjugated cholic acid and other unconjugated acids which have appropriate physiochemical properties can be extensively absorbed by this mechanism. Under normal... 

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). 

The physical chemistry of micellar structure and formation has been reviewed extensively elsewhere[40,45-47], and is only briefly summarized. The concentration at which micellar aggregation of bile salts molecules occurs (critical micellar concentration, CMC) is affected by bile salt structure, pH, temperature and a variety of other factors. Conjugated bile salts have a higher CMC than the unconjugates, and the CMC for trihydroxycholanates (cholic acid) is higher than for the dihydroxy derivatives. Among the latter, deoxy-cholate forms micelles at a lower CMC than does chenodeoxycholate. 

Elaborating a method of separation of five major unconjugated bile acids, cholic 72... 

Johns WH and Bates TR., Quantification of the binding tendencies of cholestyramine I effect of structure and added electrolytes on the binding of unconjugated and conjugated bile salt anions, /. Pharm. Sci., 58,179-183 (1969). NB These values were quoted from Ekwall P, Rosendahl T and Lofman N, Bile salt solutions. I. The dissociation constants of Bie cholic and deoxycholic acids, Acta Chem. Scand., 11,590-598 (1957). They were measured at concentrations boBi above and below Bie critical micellar concentration range. 

Enteroliths are concretions of precipitated bile acids which form in the intestinal tract and thus differ from gallstones, which consist mainly of cholesterol, bilirubin, or both. All but two enteroliths of which the composition has been determined have been found to be composed of choleic acid, a molecular coordinate complex of deoxycholic acid, and usually a fatty acid in a proportion of about 8 1. Of the remaining two, one enterolith was found in an afferent gastroenterostomy loop (84) and the other in a diverticulum of the second portion of the duodenum (85). Both of these enteroliths consisted of a mixture of unconjugated primary bile acids, cholic and chenodeoxycho-lic acids. 

---