Cholic acid, conjugates structure

The liver, and also bacteria in the small and large intestine, can cause other structural modifications to bile acids as they undergo their entero-hepatic cycle. The formation of sulfate esters, already mentioned with respect to lithocholate in Section 4.2.1, is carried out primarily in the liver in man by a sulfotransferase (Lll). Other bile acids can also be sulfoconjugated to a small extent, mainly at the 3a-hydroxyl position. Bacteria, which have been isolated anaerobically from human feces, are known to possess bile acid sulfatase activity, which removes the 3a-sul te group of chenodeoxycholic and cholic acids (H24). The action of this bacterial enzyme probably explains why only trace amounts of sul ted bile acids, which are poorly absorbed in the intestine, are detected in the feces (12). Another type of bile acid conjugate, which has been identified in the urine of healthy subjects and patients with hepatobiliary disease, is the glucuronide (A7, S41). Both the liver and extrahepatic tissues, such as the kidney and small intestinal mucosa, are capable of glucuronidation of bile acids in man (M14). 

Bile salts with a steroid structure appear to be confined to vertebrates (76). In some evolutionarily more primitive vertebrates, the major bile salts are sulfate esters of polyhydroxy C27- and C26-steroids and/or taurine-conjugated C27-steroid acids. In other primitive vertebrates, C24 bile acids, usually cholic acid and/or allocholic acid, or mixtures of primitive bile salts (bile alcohols and C27 bile acids) and modern bile salts (C24 bile acids) occur. Most of the work concerning the structure and occurrence of primitive bile salts has been carried out in the laboratories of G. A. D. Haslewood and T. Kazuno, and Haslewood and collaborators have accumu-... 

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. 

The most prominent BA present in human are cholic acid (C), chenodeoxy-cholic acid (CDC), deoxycholic acid (DC), lithocholic acid (LC), and ursodeoxycholic acid (UDC), as derivatives of 5p-cholan-24-oic acid. Primarily they are present as glycine and taurine conjugates, with the conjugation occurring at carbon 24 of the structure. In addition to the above major BA, a wide array of minor components has been identified. 

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. 

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