Bile salts action

Although both the pH and temperature have important effects on bile salt action, neither phenomenon has yet added to an understanding of the exact mechanism of the activation. 

The effect of synthetic detergents on lipase action has also been examined in an attempt to elucidate the mechanism of bile salt action. A comprehensive study was made by Wills (308), who compared several anionic, cationic, and nonionic detergents. The natural activating agents,... 

Irrespective of the physical form of the carotenoid in the plant tissue it needs to be dissolved directly into the bulk lipid phase (emulsion) and then into the mixed micelles formed from the emulsion droplets by the action of lipases and bile. Alternatively it can dissolve directly into the mixed micelles. The micelles then diffuse through the unstirred water layer covering the brush border of the enterocytes and dissociate, and the components are then absorbed. Although lipid absorption at this point is essentially complete, bile salts and sterols (cholesterol) may not be fully absorbed and are not wholly recovered more distally, some being lost into the large intestine. It is not known whether carotenoids incorporated into mixed micelles are fully or only partially absorbed. 

Hydrolysis of retinyl ester to retinol occurs in the lumen of the small intestine from where it is absorbed with the aid of bile salts, esterified to form retinyl ester and then released into lymph where it is incorporated into chylomicrons. The action of lipoprotein lipase converts chylomicrons to remnants and the retinyl ester remains in the remnants to be taken up by the Uver, where it is stored as the ester until required. On release from the liver, it is transported in blood bound to retinal binding-protein. 

Mechanism of Action An antioxidant that prevents oxidation of vitamins A and C, protects fatty acids from aff ack by free radicals, and protects RBCs from hemolysis by oxidizing agents. Therapeutic Effect Prevents and treats vitamin E deficiency. Pharmacokinetics Variably absorbed from the GI tract (requires bile salts, dietary fat, and normal pancreatic function). Primarily concentrated in adipose tissue. Metabolized in the liver. Primarily eliminated by biliary system. 

Mechanism of Action An antiulcer agent that forms an ulcer-adherent complex with proteinaceous exudate, such as albumin, at ulcer site. Also forms a viscous, adhesive barrier on the surface of intact mucosa of the stomach or duodenum. Therapeutic Effect Protects damaged mucosa from further destruction by absorbing gastric acid, pepsin, and bile salts. 

Bile salts emulsify fats in the intestine. The hydrophobic side or surface of the bile salt associates with triacylglycerols to form a complex. These complexes aggregate to form a micelle, with the hydrophilic side of the bile salt facing outward. Pancreatic lipase also associates with this micelle. The action of the lipase releases free... 

Penetration enhancers have different mechanisms of action depending on their physicochemical properties. Some examples of penetration enhancers and their mechanisms are bile salts (micellization and solubilization of epithelial lipids), fatty acids such as oleic acid (perturbation of intracellular lipids) [25,26], azone (l-dodecylazacycloheptan-2-one) (increasing fluidity of intercellular lipids), and surfactants such as sodium lauryl sulfate (expansion of intracellular spaces). The complete list of enhancers and their mechanism of actions are discussed in detail in Chapter 10. 

Initial attempts at selecting PEs have identified certain surfactants, such as bile salts and fatty acids, which appear to facilitate oligonucleotide absorption. The advantages of these components are many, in that they are endogenous to foods and body constituents, plus the literature is rich with information about the use and exposure of these two classes of compounds [56]. The precise mechanism of action for these PEs is unknown, but is believed to involve a disruption of the mucus layer barrier, an increase in the fluidity of the mucosal membrane, and potentially an opening of the paracellular tight junctions. The mucolytic effect coupled with the increased membrane fluidity imparted by these excipients appears to allow in-... 

The action of bile salts is a little like that of soap. What function do bile salts perform in the intestine Look up the action of soaps, and explain how you think bile salts may function somewhat like soap. 

A special consideration in the digestion of fats is that they are not water soluble and cannot be placed in aqueous solution along with the water-soluble lipase digestive enzymes. However, intimate contact is obtained by emulsification of fats through the action of bile salts from glycocholic and taurocholic acids produced from cholesterol in the liver ... 

HDLs have the opposite function to that of LDLs in that they remove cholesterol from the tissues. The HDLs are synthesized in the blood mainly from components derived from the degradation of other lipoproteins. HDLs then acquire their cholesterol by extracting it from cell membranes and converting it into cholesterol esters by the action of LCAT (Fig. 1). The HDLs are then either taken up directly by the liver or transfer their cholesterol esters to VLDLs, of which about half are taken up by the liver by receptor-mediated endocytosis (Fig. 1). The liver is the only organ that can dispose of significant quantities of cholesterol, primarily in the form of bile salts (see Topic K5). 

S. Iverson, C. Kirk, M. Hamosh, and J. Newsome. Milk lipid digestion in the neonatal dog the combined actions of gastric and bile salt stimulated lipases. Bhcflim, Blopkys. Ada J083 109 (1991). 

Abstract The major enzymatic barrier to the absorption of macromolecules, particularly therapeutic peptides, is the pancreatic enzymes the peptidases, nucleases, lipases and esterases that are secreted in considerable quantities into the intestinal lumen and rapidly hydrolyse macromolecules and lipids. In the case of the peptidases, they work in a co-ordinated fashion, whereby the action of the pancreatic enzymes is augmented by those in the brush borders of the intestinal cells. The sloughing-off of mucosal cells into the lumen also furnishes a mixture of enzymes that are a threat to macromolecules. As the specificity and activity of the enzymes are not always predictable, during pharmaceutical development it is important to test the stability of therapeutic macromolecules, and novel macromolecular-containing or lipid-containing formulations, in the presence of mixtures of pancreatic enzymes and bile salts, or in animal intestinal washouts or ideally, aspirates of human intestinal contents. 

Cows milk LPL has phospholipase Ai activity (Scow and Egelrud, 1976), but its action on milk phospholipids has not been recorded. Freshly secreted goats milk has been shown to have phospholipase A activity (Long and Patton, 1978) but it is not known whether this can be attributed to the LPL of that milk. Human milk contains an acid sphingomylinase C, as well as ceramidase activity provided by the bile salt-stimulated lipase present (Nyberg et al., 1998). 

The conversion of cholesterol to bile salts begins when hydroxyl groups are introduced into the phenanthrene ring of cholesterol by the action of cholesterol 7-a-hydroxylase, followed by modification of the side chain. Cholic acid and chenodeoxycholic acid are produced, as shown in Fig. 13-24. 

Lipases. Some lipases, especially the bile-salt-stimulated lipases in human milk, destroy the protozoan Giardia Iambiia (58) The free fatty acids are responsible for the action. This was shown by the requirement for incubation of the cream with the skim to develop the inhibitor. Studies with the addition of Giardia to milk (59) showed that preincubation was necessary to get a good kill of the added cells. There was substantially no change in viable count without cholate, whereas with cholate the viable count went to virtually zero over the two hours. 

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