Bile salts,

Enhanced solubility of the low water-soluble drug may be obtained by bile salts through the wetting mechanism [36, 37]. This is the main mechanism when the bile salts are present at a level below their CMC [35, 38]. 

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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 structure of cholic acid helps us understand how bile salts such as sodium tauro cholate promote the transport of lipids through a water rich environment The bot tom face of the molecule bears all of the polar groups and the top face is exclusively hydrocarbon like Bile salts emulsify fats by forming micelles m which the fats are on the inside and the bile salts are on the outside The hydrophobic face of the bile salt associates with the fat that is inside the micelle the hydrophilic face is m contact with water on the outside... 

The mechanism by which sucralfate accelerates healing of duodenal ulcers has not been determined. It does not have significant antisecretory, acid neutralizing activity or direct stimulation of ulcer healing. It is known that the mechanism is local rather than systemic. Binding of pepsin or bile salts may contribute to its effect. It is indicated for the short-term therapy of active duodenal ulcers and for maintenance at reduced dosage. 

Bde salts, cholesterol, phosphoHpids, and other minor components are secreted by the Hver. Bile salts serve three significant physiological functions. The hydrophilic carboxylate group, which is attached via an alkyl chain to the hydrophobic steroid skeleton, allows the bile salts to form water-soluble micelles with cholesterol and phosphoHpids in the bile. These micelles assist in the solvation of cholesterol. By solvating cholesterol, bile salts contribute to the homeostatic regulation of the amount of cholesterol in the whole body. Bile salts are also necessary for the intestinal absorption of dietary fats and fat-soluble vitamins (24—26). 

Clinical stresses which interfere with vitamin metabohsm, can result in calcium deficiency leading to osteomalacia and osteoporosis (secondary vitamin D deficiency). These stresses include intestinal malabsorption (lack of bile salts) stomach bypass surgery obstmctive jaundice alcoholism Hver or kidney failure decreasing hydroxylation of vitamin to active forms inborn error of metabohsm and use of anticonverdiants that may lead to increased requirement. 

Dietary fiber and fiber-rich food fractions bind bile acids and bile salts in vitro. This interaction is more pronounced for the lignin component. 

Entozyme 18/100 Digestive enymes pancreatin/pepsin/bile salts Robins... 

Pancrease 30/100 pancreatin/pepsin/bile salts McNeil... 

Tlozyme 77/250 pancreatin/pepsin/bile salts Adtia... 

Resistant to ether, chloroform, and bile salts, indicating lack of essential lipids... 

FIGURE 24.4 In the small intestine, fatty acids combine with bile salts in mixed micelles, which deliver fatty acids to epithelial cells that cover the intestinal villi. Triacylglycerols are formed within the epithelial cells. 

We turn now to the biosynthesis of lipid structures. We begin with a discussion of the biosynthesis of fatty acids, stressing the basic pathways, additional means of elongation, mechanisms for the introduction of double bonds, and regulation of fatty acid synthesis. Sections then follow on the biosynthesis of glyc-erophospholipids, sphingolipids, eicosanoids, and cholesterol. The transport of lipids through the body in lipoprotein complexes is described, and the chapter closes with discussions of the biosynthesis of bile salts and steroid hormones. 

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. 

FIGURE 25.41 Cholic acid, a bile salt, is synthesized from cholesterol via 7o -hydroxy-cholesterol. Conjugation with taurine or glycine produces taurocholic acid and glycocholic acid, respectively. Taurocholate and glycocholate are freely water-soluble and are highly effective detergents. 

Because they contain both nonpolar and polar domains, these bile salt conjugates are highly effective as detergents. These substances are made in the liver, stored in the gallbladder, and secreted as needed into the intestines. 

Some examples of sterols and steroids are given in Figure 9.1. Also included in this Figure are some examples of bile salts. You should realise that the structures shown are only a few of the many hundreds of compounds which occur in nature. All of these compounds include the steroidal ring structure which is numbered as shown below. 

In general, the sterols perform a structural function, for example as components of the lipid layers of membranes. The Cis, C19 and C21 steroids mainly perform an endocrine function. In other words they are hormones. The bile salts (C24-steroids) fulfil a functional role in digestion in animals. 

Again, the answer should be fairly obvious. The potential therapeutic value of the steroid hormones makes these of tremendous commercial value. The commercial market for these is of the order of hundreds of millions of dollars per year. There is no comparable market for sterols and bile salts. We are faced with the interesting situation, therefore, that sterols are relatively abundant in natural sources but of relatively low commercial value, whilst steroids occur naturally at very low concentrations but are of great commercial value. Although there are tremendous variations amongst different products, steroids with desirable properties command market prices that are (ten to one thousand fold) greater than their sterol counterparts. 

A medium containing bile salts such as lithocholic add along with carbohydrates and peptone has been used to isolate gut organisms. One such isolate has been shown to completely degrade the lithocholic add (structure given in Figure 9.1). 

MRP1 (ABCC1) Glucuronides and sulfate conjugates of steroid hormones and bile salts, colchicine, doxorubicin, daunorubicin, epirubicin, folate, irinotecan, methotrexate, pacitaxel, vinblastine, vincristine, and others... 

MRP2 (ABCC2) LTC4, bilirubin-glucuronide, estradiol 17 3-glucuronide, dianionic bile salts, anionic conjugates, glutathione disulfide, and others... 

MRP3 (ABCC3) Organic anions including bile salts... 

Houten SM, Auwerx J (2004) The enterohepatic nuclear receptors are major regulators of the enterohepatic circulation of bile salts. Ann Med 36 482-491... 

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