Cholic acid, bile salt metabolism

Part of the cholesterol newly synthesized in the liver is excreted into bile in a free non-esterified state (in constant, amount). Cholesteiol in bile is normally complexed with bile salts to form soluble cholic acids, Free cholesterol is not readily soluble and with bile stasis or decreased bile salt concentration may precipitate as gallstones. Most common gallstones are built of alternating layers of cholesterol and calcium bilirubin and consist mainly (80-90%) of cholesterol. Normally. 80% of hepatic cholesterol arising from blood or lymph is metabolized to cholic acids and is eventually excreted into the bile in the form of bile salts. 

Rosinate and Cholate. These carboxylates were included because of their different (from fatty acid) structure rosin acids compose about half of the tall oil acids and cholic acid is a representative bile acid that is important in the animal metabolism of fats. Salts of these acids had interfacial tensions that were significantly higher than oleate no minima were found (Figure 7)-... 

Taurine is a by-product of cysteine metabolism. Taurine is conjugated to cholic acid to form taurocholate, a bile salt. 

Colonic reabsorption of secondary bile acids seems to be clearly established. The presence of deoxycholic acid as a normal biliary constituent indicates that it has been absorbed from the colon. Furthermore, the human bile contains a variety of other bacterial transformation products such as lithocholic acid and other cholanic acids, some of which may have been further metabolized by the liver (44-47). In contrast to the case in some other mammalian species, human liver is not able to convert deoxycholic acid back to cholic acid. Colonic perfusion with different labeled bile acids has clearly shown that colonic absorption takes place in man (48). Administration of labeled cholic acid into the lumen of the large bowel during operation for cholecystectomy is followed by the appearance of labeled cholic acid and deoxycholic acid in the T-tube bile, the recovery from the T-tube being about 60% of the dose (49). This clearly shows that cholic acid is converted to deoxycholic acid in the human colon and that both of them are absorbed from the large bowel. Colonic reabsorption has been calculated to amount to 200 mg/ day (49). The colonic absorption of secondary bile salts could be even higher if the physical state of some bile acids were not unfavorable for absorption. Lithocholic acid, for example, is a very nonpolar compound and precipitates in the colonic content in addition, it and other secondary bile acids as well are partially associated with fecal debris and bacteria (41). As a result of poor absorption, the amount of secondary bile acids, other than deoxycholic acid, is usually low in human bile. After a continuous biliary drainage, secondary bile acids disappear from the bile in a few days (49-51). 

In the isotope dilution method, described originally by Lindstedt (35), a tracer dose of a labeled bile acid is given orally or intravenously and the disappearance is followed by determining the specific activity of that bile acid in duodenal contents serially for up to 7 days. The specific activitytime curve is exponential. Thus the pool size and turnover (equals synthesis) of that bile salt can be determined. Cholic and chenodeoxycholic acids appear to have slightly different turnover data in some individuals (38,67). Therefore, the metabolism of the two should be measured separately if exact figures are wanted, by using both labeled cholic and chenodeoxycholic acids. A gross estimate of the one can be obtained, however, from the ratio of these two bile acids in the bile if the pool and turnover of the other are measured (35,37). 

Figure 19.10 shows a structural formula for cholic acid, a constituent of human bile. The molecule is shown as an anion, because it would be ionized in bile and intestinal fluids. Bile acids, or, more properly, bile salts, are synthesized in the liver, stored in the gallbladder, and secreted into the intestine, where their function is to emulsify dietary fats and thereby aid in their absorption and digestion. Furthermore, bile salts are the end products of the metabolism of cholesterol and, thus, are a principal pathway for the elimination of that substance from the body. A characteristic structural feature of bile salts is a cis fusion of rings A/B. 

The size of the bile acid pool in the rat is about 14—20 mg, but may vary with the diet, being lower when semi-synthetic diets are fed (Eriksson, 1960 PoRTMAN and Murphy, 1958). The half life of cholic and chenodeoxycholic acids is 2—3 days in normal rats (Lindstedt and Norman, 1956), but is much higher in the absence of intestinal microorganisms (Lindstedt and Norman, 1956 Gustafsson et al., 1957). The intestinal flora hydrolyze the circulating bile salts and, normally, only free bile acids are found in the feces. Thyroid hormone exerts a marked effect on bile acid metabolism. In the euthyroid rat the cholic chenodeoxy cholic ratio is 4 1, but this is almost reversed in the hyperthyroid rat (Eriksson, 1957). The thyroid effect appears to be an inhibition of the 12a-hydroxylase, since the extent of side chain oxidation of cholesterol-26-is the same in eu-, hyper-, or hypothyroid rats (Kritchevsky et al., 1962). 

The primary bile salts (those synthesized in the liver) are conjugates of chenodeoxycholic acid and cholic acid with taurine or glycine (Figure 4.16). Intestinal bacteria catalyse deconjugation and further metabolism to yield the secondary bile... 

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