Bile acids, also

Bile acids also yield fluorescence when an only 5% perchloric acid is employed as reagent and the chromatogram is only heated to 100°C until coloration commences [9]. Steroids can also be detected with 2% methanohc perchloric acid [4]. 

Kandell and Bernstein published one of the earliest reports to suggest that bile acids also demonstrate DNA-damaging effects in eukaryotic cells. They showed that human foreskin fibroblasts underwent unscheduled DNA synthesis (indicating DNA repair), as measured by tritiated thymidine incorporation when cells were treated with increasing concentrations of sodium deoxycholate or chenodeoxycholate. Utilising mutant Chinese hamster ovary cells deficient in strand rejoining (EM9), the authors were able to demonstrate that the repair of deoxycholate-induced DNA damage was dependent on strand break repair capacity. 

Functioning as detergents, hydrophobic (Hpophiiic) bile acids (cholic add, chenodeoxycholic add, deoxychohc add, hthochohc acid) exert toxic efifects on the biomembranes of liver cells and mitochondria. At the same time, these bile acids display an immunosuppressive elfect and influence the humoral and cell-mediated defence (e.g. inhibition of monocytes). As in the case of PBC, hydrophobic bile acids also induce an excessive expression of MHC-I and MHC-II molecules from hepatocytes and bihary cells. 

On the basis of surface and bulk interaction with water. Small [85] classified bile acids as insoluble amphiphiles and bile salts as soluble amphiphiles. On account of the undissociated carboxylic acid group, the aqueous solubility of bile acids is limited [35] in contrast, many bile salts have high aqueous solubilities as monomers [33] and, in addition, their aqueous solubilities are greatly enhanced by the formation of micelles [5,6]. Because many bile salts are weak electrolytes, their ionization and solubility properties are more complicated than those of simple inorganic or organic electrolytes [5,35]. For example, the p/Tj, values of bile acids in water vary markedly as functions of bile salt concentration and, because micelles formed by the A (anionic) species can solubilize the HA (acid) species [5,35], the equilibrium precipitation pH values of bile acids also vary as functions of bile salt concentration. Finally, certain bile salts are characterized by insolubility at ambient temperatures [2,5,6,86,87], only becoming soluble as micelles at elevated temperatures (the critical micellar temperature) [6]. 

The role of bile acids in the absorption of other lipids such as cholesterol, fat-soluble vitamins, and fat-soluble drugs is similar to that described for fat (2). Bile acids are considered to influence the rate of hydrolysis of ingested cholesterol esters by interacting with cholesterol esterase and protecting it from tryptic digestion (86). Bile acids also influence the cleavage rate of / -carotene (87) conceivably, this effect is mediated on the surface of the cell. 

The negative correlation between fecal bile acids and serum cholesterol was of low degree for the total series (r = —0.24) and for nonobese patients (r = —0.27), the correlation being positive with the serum cholesterol pool (r = 0.28). Fecal bile acids also correlated positively with body weight (r = 0.52), relative body weight (r = 0.31), and body surface (r = 0.53). 

The bile acids are produced from cholesterol in the liver and stored in the gallbladder. The primary human bile acid is cholic acid (Figure 21.25h), a substance that aids in the digestion of fats by emulsifying them in the intestine. Bile acids also can dissolve cholesterol ingested in food and are therefore important in controlling cholesterol in the body. 

Cholic (III) and chenodesoxycholic (VII) acids (Fig. 5), two of the common primary bile acids, undergo further chemical alterations by the action of microbial flora in the gut to give rise to several secondary bile acids (also possessing 24 carbon atoms), such as desoxycholic (VIII), hyodesoxy-cholic (IX), and lithocholic (X) acids (Fig. 5). 

Figure 4 Peroxisomal fatty-acid (FA) /3-oxidation pathways. While saturated long-chain fatty acids (LCFA) are preferentially degrade in mitochondria, saturated very-long-chain fatty acids (VLCFA) and some LCFA are shortened by peroxisomal /3-oxidation. Degradation of pristanic acid, the product of phytanic acid a-oxidation, and the conversion of the cholesterol-derived 27-carbon bile-acid precursors dihydroxycholestanoic acid (DHCA) and trihydroxycholestanoic acid (THCA) to 24-carbon bile acids also require this pathway. The mechanism by which these substrates enter peroxisomes is unknown. Four enzymatic reactions serve to shorten the substrates by either two (LCFA, VLCFA) or three (pristanic acid, DHCA, THCA) carbon atoms. The 2-methyl group of the latter substrates is shown in brackets. SCPx thiolase refers to the thiolase activity of sterol carrier protein x.

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