Bile acids functions

Houten SM, Watanabe M, Auwerx J (2006) Endocrine functions of bile acids. EMBO J 25 1419-1425... 

CYP27A1 catalyzes the side chain oxidation (27-hydroxylation) in bile acid biosynthesis. Because bile acid synthesis is the only elimination pathway for cholesterol, mutations in the CYP27A1 gene lead to abnormal deposition of cholesterol and cholestanol in various tissues. This sterol storage disorder is known as cerebrotendinous xanthomatosis. CYP27B1 is the 1-alpha hydroxylase of vitamin D3 that converts it to the active vitamin form. The function of CYP27C1 is not yet known. 

Hagenbuch, B. and P. J. Meier. Molecular cloning, chromosomal localization, and functional characterization of a human liver Na+/ bile acid cotransporter. J. Clin. Invest. 1994, 93, 1326-1331. 

Alpini, G., et al. Functional expression of the apical Na+-dependent bile acid transporter in large but not small rat cholangiocytes. Gastroenterology... 

Hagenbuch, B., et al. Functional expression cloning and characterization of the hepatocyte Na+/bile acid cotransport system. Proc. Natl. Acad. Sci. U. S. A. 1991, 88, 10629-10633. 

Chignard N, Mergey M, Veissiere D, Parc R, Capeau J, Poupon R et al. Bile acid transport and regulating functions in the human biliary epithelium. Hepatology 2001 33(3)496-503. 

The answer is a. (Katzung, p 590.) Bile acids are absorbed primarily in the ileum of the small intestine. Cholestyramine binds bile acids, preventing their reabsorption in the jejunum and ileum. Up to 10-fold greater excretion of bile acids occurs with the use of resins. The increased clearance leads to increased cholesterol turnover of bile acids. Low-density lipoprotein receptor upregulation results in increased uptake of LDL. This does not occur in homozygous familial hypercholesterolemia because of lack of functioning receptors. 

Zhang, J., Huang, W., Qatanani, M., Evans, R.M. and Moore, D.D. (2004) The constitutive androstane receptor and pregnane X receptor function coordinately to prevent bile acid-induced hepatotoxicity. Journal of Biological Chemistry, 279, 49517 19522. 

A pharmacophore model for FXR agonists based on 14 bile acid derivatives was reported by Ekins et al. The hypothesis consisted of three H features and one H BA - a common functionality pattern among steroidal compounds [42],... 

Studies in experimental animals suggest that biliary excretion of chemicals from the liver may be impaired by mirex or chlordecone (Berman et al. 1986 Curtis and Hoyt 1984 Curtis and Mehendale 1979 Curtis et al. 1979b, 1981 Davison et al. 1976 Mehendale 1976, 1977b, 1977c, 1981b Teo and Vore 1991). Measurement of serum bile acid levels may provide information regarding biliary excretory function. 

Teo S Vore M. 1991. Mirex inhibits bile acid secretory function in vivo and in the isolated perfused rat liver. Toxicol Appl Pharmacol 109(1) 161-170. 

Putnam, W.S., Ramanathan, S., Pan, L., Takahashi, L.H., and Benet, L.Z., Functional characterization of monocarboxylic acid, large neutral amino acid, bile acid and peptide transporters, and P-glycoprotein in MDCK and Caco-2 cells, /. Pharm. Sci., 91, 2622, 2002. 

Endogenous and exogenous androgens can be derivatized with trimethylsilyl (TMS) for hydroxy functions and by 0-methylation for ketones, and analyzed with GC-FID or GC-MS (Shimada et al., 2001). MS is more prevalent due to unequivocal identification and greatly increased sensitivity but FID is still used in laboratories for some steroids. Sterols have typically been analyzed by GC-FID and GC-MS with derivatization to optimize peak shape (Shimada et al., 2001), and bile acids can be derivatized with M-butyl ester-TMS ether and analyzed by GC-FID from plasma samples (Batta et al., 1998). Juricskay and Telegdy (2000) reported an assay capable of analyzing 28 steroids in urine samples using GC-FID. 

Other Toxicity Concerns. Additional toxicity concerns include interference with normal metabolism and function of mucosal cells, for example, water absorption by these cells [80]. The unconjugated bile acids are known to block amino acid metabolism [81] and glucose transport [82]. There is a possibility of biotransformation of these enhancers to toxic or carcinogenic substances by hepatic monooxygenases [83]. Absorption of permeation enhancers into the systemic circulation can also cause toxicity, for example, azone [84] and hexamethylene lauramide [85] which are absorbed... 

An Overview of Bile-Acid Synthesis, Chemistry and Function... 

E. Scotti, F. Gilardo, C. Godio, E. Gers, J. Krneta, N. Mitro, E. De Fabiano, D. Caruso and M. Crestani, Bile acids and their signalling pathways eclectic regulators of diverse cellular functions. Cell Mol. Life Sci., 2007, 64, 2477-2491. 

Vesicular transport of bile acids has not been demonstrated under normal conditions, shown by using isolated rat hepatocyte couplets and fluorescently labelled bile acids. In these experiments confocal microscopy found no evidence of sequestering into clusters and colchicine disruption of microtubular function did not affect bile-acid transport. This makes it unlikely that vesicle transport plays a role and it is now believed that bile acids traverse the hepatocyte by diffusion through the cytosol while bound to soluble proteins. It is worth considering the caveat that fluorescently labelled bile acids, while very useful tools, do differ structurally from endogenous bile acids with increased hydro-phobicity leading to greater retention by cells. ... 

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