Conjugation of bile salts

Vossey, D. A- (1978). The biochemicai basis for the conjugation of bile. salts with cither glycine or taurine. Biocheoi. J. 174, 621-626. 

Sulfate conjugates of bile salts taurolithocholate sulfate... 

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.

The most active subcellular fraction for conjugation of bile salt CoA intermediates with taurine or glycine is microsomal (32). The system is strongly stimulated by the addition of a lysosome fraction, which may contain some peroxisome particles (33). Taurine and glycine are the only amino acids known to conjugate with bile acids in man, and the conjugation appears to be limited to the liver. In healthy adults, the usual glycine/taurine ratios are... 

This paper reports the systematic study of the apparent anhydrous micellar weights of the three principal bile salts found in man and their glycine and taurine conjugates in respect to bile salt concentration, counterion concentration, temperature, pH, and urea concentration. On the basis of these studies, model structures of bile salt micelles are proposed. Sodium dehydrocholate, a triketo bile salt, was also studied but was not found to form micelles. 

Effect of pH. The effect of pH on the deoxycholate series of bile salts in 0.15N NaCl at 20° and 36°C. is summarized in Figure 8. Solutions of free and glycine conjugated bile salts were studied between pH 9.2 and their precipitation pH (NaDC == 6.95, NaGDC = 4.9). Taurine conjugates were studied between pH 10 and 1.6. 

Bile salts secreted into the intestine are efficiently reabsorbed (greater than 95 percent) and reused. The mixture of primary and secondary bile acids and bile salts is absorbed primarily in the ileum. They are actively transported from the intestinal mucosal cells into the portal blood, and are efficiently removed by the liver parenchymal cells. [Note Bile acids are hydrophobic and require a carrier in the portal blood. Albumin carries them in a noncovalent complex, just as it transports fatty acids in blood (see p. 179).] The liver converts both primary and secondary bile acids into bile salts by conjugation with glycine or taurine, and secretes them into the bile. The continuous process of secretion of bile salts into the bile, their passage through the duodenum where some are converted to bile acids, and their subsequent return to the liver as a mixture of bile acids and salts is termed the enterohepatic circulation (see Figure 18.11). Between 15 and 30 g of bile salts are secreted from the liver into the duodenum each day, yet only about 0.5 g is lost daily in the feces. Approximately 0.5 g per day is synthesized from cholesterol in the liver to replace the lost bile acids. Bile acid sequestrants, such as cholestyramine,2 bind bile acids in the gut, prevent their reabsorption, and so promote their excretion. They are used in the treatment of hypercholesterolemia because the removal of bile acids relieves the inhibition on bile acid synthesis in the liver, thereby diverting additional cholesterol into that pathway. [Note Dietary fiber also binds bile acids and increases their excretion.]... 

Studies by Hall et al (1979) have shown that the bile-activated enzyme can be stimulated fifty-fold by freezing and thawing, by Bonification, or by addition of bile salt addition of glycine conjugate was four times more effective than addition of taurine conjugate. Studies on the kinetic and chemical characterization of the enzyme were performed by Wang (1981). 

Ross, B. P., A. C. Braddy, R. P. McGeary, J. T. Blanch eld, L. Prokai, and I. Toth. 2004. Micellar aggregation and membrane partitioning of bile salts, fatty acids, sodium dodecyl sulfate, and sugar-conjugated fatty acids Correlation with hemolytic potency and implications for drug delivbtpl. Pharm. 1 233-245. 

The common bile salts in humans are glycine and taurine conjugates of sodium deoxycho-late (NaDOC) and sodium chenodeoxycholate (CDOC), dihydroxy bile salts, and sodium cholate (NaC, the trihydroxy bile salt). The ability of bile salts to increase transmucosal transport of solutes has been frequently stated [62,81,82]. Generally, the more hydrophobic dihydroxy bile salts act as more effective absorption enhancers in comparison to trihydroxy bile salts. For example, Gullikson et al. [83] have reported that the absorption of inulin, dextran, and albumin in the perfused rat jejunum was enhanced with dihydroxy but not with trihydroxy bile salts. 

Conjugated bile salts are normally absorbed in the terminal ileum. Disease of the terminal ileum (eg, Crohn s disease) or surgical resection leads to malabsorption of bile salts, which may cause colonic secretory diarrhea. The bile salt binding resins cholestyramine or colestipol may decrease diarrhea caused by excess fecal bile acids (see Chapter 35 Agents Used in Hyperlipidemia). The usual dose is 4-5 g one to three times daily before meals. Side effects include bloating, flatulence, constipation, and fecal impaction. In patients with diminished circulating bile acid pools, further removal of bile acids may lead to an exacerbation of fat malabsorption. These agents bind a number... 

The bile acids produced by the liver accumulate in the gall bladder in the form of bile salts they are bile acids in which the carboxylic acid group is conjugated with glycine or taurine. 

The enhancement of nasal absorption of insulin by hydrophobic bile salts has also been investigated. It was found that minor differences in the number, position, and orientation of the nuclear hydroxyl groups as well as alterations to side-chain conjugation can improve the adjuvant potency of bile salts. Moreover, the absorption of insulin positively correlated with an increase in the hydrophilicity of the steroid nucleus of the bile salts. In the presence of bile salts, nasal absorption of insulin reached peak levels within about lOmin, and some 10-20% of the dose was found to have been absorbed into the circulation. Marked increases in serum insulin levels were seen with sodium deoxycholate, the most lipophilic of the bile salts, whereas the least elevation—as well as least lowering of blood glucose levels—was seen with the most hydrophobic bile salt, sodium ursodeoxycholate [63],... 

Menaquinones are absorbed mainly from the terminal ileum, where bile salts are present, into the hepatic portal vein. Litde of the menaquinones formed by colonic bacteria can be absorbed, because they remain tightly bound to bacterial cell membranes in the absence of bile salts. About 90% of the total liver content of vitamin K is menaquinones 7 to 13, and the hepatic pool of phylloquinone turns over considerably faster than that of menaquinones. Sixty percent to 70% of the daily intake of phylloquinone is excreted, mainly as conjugates in the bile, and the half-life of a tracer dose of phylloquinone is only about 17 hours. 

---