Bile derivatives

As pointed out by Dixon and colleagues if a direct role for refluxed bile derivatives in carcinogenesis becomes accepted, therapy aimed principally at acid reduction, cannot be expected to eliminate cancer risk in Barrett s oesophagus. However, not only is acid suppression likely to be ineffective in preventing bile acid-driven carcinogenesis, it could also actually promote cancer development by providing a less acidic environment favouring bile acid activity. 

For the differentiation of the alcohol- from the bile-derived etiology of AP, the lipase/cy-amylase ratio (L/A) has been introduced. To determine an optimal cutoff value is, however, somewhat difficult. Gumaste el al. (G13) proposed L/A > 2 for alcoholic AP and L/A < 2 for the biliary etiology of AP (sensitivity 84%, specificity 89%), whereas Tenner and Steinberg (T5, S20) and Kazmierczak el al. (K4) suggested significant L/A ratios of 4.0 and 4.2, respectively (Table 2). 

In the lumen of the small intestine, dietary fat does not only meet bile salt but the much more complex bile in which bile salts are about half saturated with lecithin in a mixed micellar system of bile salt-lecithin-cholesterol. On dilution in the intestinal content, the micelles grow in size as the phase limit is approached and large disk-like micelles form which fold into vesicles [49]. These changes are due to the phase transition that occurs when the bile salt concentration is decreased and the solubility limit for lecithin in the mixed micelles is exceeded. The information is mostly derived from in vitro studies with model systems but most probably is applicable to the in vivo situation. What in fact takes place when the bile-derived lamellar bile salt-lecithin-cholesterol system meets the partly digested dietary fat can only be pictured. Most probably it involves an exchange of surface components, a continuous lipolysis at the interphase by pancreatic enzymes and the formation of amphiphilic products which go into different lamellar systems for further uptake by the enterocyte. Due to the relatively low bile salt concentration and the potentially high concentration of product phases in intestinal content early in fat digestion, the micellar and monomeric concentration of bile salt can be expected to be low but to increase towards the end of absorption. 

Biological products, products of animal or human origin including vaccines, serums, blood, animal bile derivatives, endocrine products, etc. 

A significant fraction of the body s cholesterol is used to form bile acids Oxidation m the liver removes a portion of the CsHi7 side chain and additional hydroxyl groups are intro duced at various positions on the steroid nucleus Cholic acid is the most abundant of the bile acids In the form of certain amide derivatives called bile salts, of which sodium tau rocholate is one example bile acids act as emulsifying agents to aid the digestion of fats... 

The outer layer or cortex of the adrenal gland is the source of a large group of sub stances known as corticosteroids Like the bile acids they are derived from cholesterol by oxidation with cleavage of a portion of the alkyl substituent on the D ring Cortisol IS the most abundant of the corticosteroids but cortisone is probably the best known Cortisone is commonly prescribed as an antiinflammatory drug especially m the treat ment of rheumatoid arthritis... 

Bile acids (Section 26 13) Steroid derivatives biosynthesized in the liver that aid digestion by emulsifying fats Bimolecular (Section 4 8) A process in which two particles re act in the same elementary step Biological isoprene unit (Section 26 8) Isopentenyl pyrophos phate the biological precursor to terpenes and steroids... 

Choline base [123-41 -17, [(CH2)3NCH2CH20H] 0H, triniethyl(2-hydroxyethyl)-ammonium hydroxide, derives its name from bile (Greek chole from which it was first obtained. This so-called free-ch oline is a colorless, hygroscopic Hquid with an odor of trimethyl amine. The quaternary ammonium compound (1) choline [62-49-7] or a precursor is needed in the diet as a constituent of certain phosphoHpids universally present in protoplasm. 

A number of steroids have been regioselectively acylated ia a similar manner (99,104). Chromobactenum viscosum hpase esterifies 5a-androstane-3P,17P-diol [571-20-0] (75) with 2,2,2-triduoroethyl butyrate ia acetone with high selectivity. The hpase acylates exclusively the hydroxy group ia the 3-position giving the 3P-(monobutyryl ester) of (75) ia 83% yield. In contrast, bacillus subtilis protease (subtihsia) displays a marked preference for the C-17 hydroxyl. Candida iylindracea]i 2Lse (CCL) suspended ia anhydrous benzene regioselectively acylates the 3a-hydroxyl group of several bile acid derivatives (104). 

Bile acids (Section 26.13) Steroid derivatives biosynthesized in the liver that aid digestion by emulsifying fats. 

Bile acids, which exist mainly as bile salts, are polar carboxylic acid derivatives of cholesterol that are important in the digestion of food, especially the solubilization of ingested fats. The Na and salts of glycocholic acid and tauro-cholic acid are the principal bile salts (Ligure 25.41). Glycocholate and tauro-cholate are conjugates of cholic acid with glycine and taurine, respectively. 

Shimomura, O. (1980). Chlorophyll-derived bile pigment in bioluminescent euphausiids. FEBS Lett. 116 203-206. 

Host-derived (e.g., antigen-antibody complexes, activated complement fragments, inflammatory bile acids, urate crystals, certain androgenic steroid metabolites [e.g., etiocholanolone], certain lymphocyte products)... 

PPARa Liver, heart, skeletal muscle, atherosclerotic lesions TG- and LDL-C-lowering and HDL-C-raising re-directs excess cholesterol from the peripheral tissues to the liver for excretion into the bile via HDL-C slowed progression of atherosclerosis Fatty acids, eico-sanoids (fatty acids derived from FAS ) Fibrates fenofibrate (Tricor ), genfibrozil (Lopid ) Dyslipidemia... 

Studies on the Antibacterial Properties of the Bile Acids and Some Compounds Derived from Cholanic Acid, M. Stacey and M. Webb, Proc. R. Soc., Ser. B, 134 (1947) 523-537. 

The sheer complexity of environmental mixtnres of EDCs, possible interactive effects, and capacity of some EDCs to bioaccumulate (e.g., in fish, steroidal estrogens and alkylphenolic chemicals have been shown to be concentrated up to 40,000-fold in the bile [Larsson et al. 1999 Gibson et al. 2005]) raises questions about the adequacy of the risk assessment process and safety margins established for EDCs. There is little question that considerable further work is needed to generate a realistic pictnre of the mixture effects and exposure threats of EDCs to wildlife populations than has been derived from studies on individual EDCs. Further discussion of the toxicity of mixtures will be found in Chapter 2, Section 2.6. 

This benign autosomal recessive disorder consists of conjugated hyperbilirubinemia in childhood or during adult life. The hyperbilirubinemia is caused by mutations in the gene encoding MRP-2 (see above), the protein involved in the secretion of conjugated bilirubin into bile. The centrilobular hepatocytes contain an abnormal black pigment that may be derived from epinephrine. 

In phase 1 reactions, xenobiotics are generally converted to more polar, hydroxylated derivatives. In phase 2 reactions, these derivatives are conjugated with molecules such as glucuronic acid, sulfate, or glutathione. This renders them even more water-soluble, and they are eventually excreted in the urine or bile. 

Vitamin D3 enters the skin microcirculation after formation and is bound to a specific globulin in the serum. It and vitamin D2 which is absorbed from the gut are subsequently metabolized to the 25-hydroxy derivative (25-OH-D) in the liver by an enzyme system which may or may not be regulated. The subsequent release of 25-OH-D from the liver is not well understood. There is evidence that it is secreted into the bile and subsequently reabsorbed by the intestine. The relative importance of this "enterohepatic" process and the release of this metabolite directly into the circulation from the liver is not known (26). 

Isolation and purification of amitriptyline, nortriptyline, and 10-hydroxy (lO-OH) derivatives of the drugs from rat bile... 

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