Biliary micelles

Both micelles and unilamellar liquid-crystalline vesicles coexist during human fat digestion in the aqueous portions of upper intestinal content [262,263, Chapter 14]. In terms of composition and size, the micelles are not like biliary micelles, as has been traditionally believed, but are considerably larger 100 A) with relative lipid compositions which fall on the limits of the mixed lipids/Ch-BS phase boundary. The liquid-crystalline vesicle (or liposomal) phase of upper small intestinal contents is less well defined physico-chemically [262,263] its crucial importance in fat digestion and absorption is obvious in view of the fact that fat absorption proceeds efficiently in the total absence of BS micelles [262]. 

At the same time the pancreatic enzymes start the cleavage of triglycerides (to mono, diglycerides and fatty acids), of cholesterol esters and of lecithin (to lysolecithin and fatty acids). As the digestion progresses bile is diluted and micelles enlarge since they include the products of lipolysis thus, intestinal micelles are markedly different, in size and composition, from biliary micelles. 

Highly insoluble molecules are in part transported in the GIT by partitioning into the mixed micelles injected into the lumen from the biliary duct in the duodenum (Fig. 2.3). Mixed micelles consist of a 4 1 mixture of bile salts and phospholipids (Fig. 7.13). In contrast, at the point of absorption in the BBB, highly insoluble molecules are transported by serum proteins. This distinction is expected to be important in in vitro assay modeling. The use of simulated intestinal fluids is appealing. 

Figure 2.2 Secretion of bile acids and biliary components. Bile acids (BA) cross the hepatocyte bound to 3a-hydroxysteroid dehydrogenase and are exported into the canaliculus by the bile-salt export protein (BSEP). Phosphatidylcholine (PC) from the inner leaflet of the apical membrane is flipped to the outer layer and interacts with bile acids secreted by BSEP. BA, PC, together with cholesterol from the membrane form mixed micelles that are not toxic to epithelial membranes of the biliary tree. Aquaporins (AQP) secrete water into bile.

Bile acids have long been known to aid digestion of dietary fats, but are not essential. Some 50% of dietary fats are absorbed in rats where bile acids are diverted by biliary fistula.Similar results were found in man. This suggested that the micellar phase isolated by ultracentrifugation of duodenal contents was in fact composed of both bile-acid micelles and vesicles, a suggestion supported by a systematic study of the physical chemistry of fat digestion in human small bowel. 

Samples of gallbladder bile obtained in this way were analysed for bile acids, phospholipids and cholesterol (from which the cholesterol saturation indices were derived). Biliary bile-acid composition was then measured by HPLC. The vesicles were separated from micelles by sucrose density gradient ultra-centrifugation and the cholesterol microcrystal nucleation time measured as described above. 

NA Mazer, GB Benedeck, MC Carey. Quasielastic light-scattering studies of aqueous biliary lipid systems. Mixed micelles formation in bile salt-lecithin solutions. Biochemistry 19 601-615, 1980. 

Biliary cholesterol is entirely unesterified and flows into the small intestine as a component of bile. The other major components of bile are phosphatidylcholine (lecithin) and bile acids. Absorption of cholesterol and other lipids depends on their ability to form micelles within the intestinal lumen. 

PBS and gently blotted to remove blood and tissue fluids, then suspended over the lip of a small (250 pi) microcentrifuge tube and punctured with a needle to allow the bile to drain into the tube. Store frozen until assay. There is usually enough material to measure lipid composition (bile acids, cholesterol, phospholipids) with standard colorimetric kits (<1 pi needed for each assay). In addition to biliary cholesterol levels, it is important to take note of bile salt concentrations, since these are the detergents which suspend dietary lipids in micelles and deliver them to the intestinal epithelium for absorption by enterocytes. Differences in bile salt concentration alone could lead to differences in cholesterol absorption. 

Disturbed secretion of bile acids Impaired fat solubilization, decreased formation of micelles Primary biliary cirrhosis Primary sclerosing cholangitis... 

Recent physical-chemical observations on native mammalian systems reveal that the proposed mixed micellar mechanism of lipid solubilization and transport in both bile and in upper small intestinal contents is incomplete [1,260-263]. Bile is predominantly a mixed micellar solution but, particularly when supersaturated with Ch, also contains small liquid-crystalline vesicles which, as suggested from model systems [239], are another vehicle for Ch and L transport. In dog bile which is markedly unsaturated with Ch [258], these vesicles exist in dilute concentrations and may be markers of the detergent properties of BS on the cells lining the biliary tree and/or related to the mode of bile formation at the level of the canaliculus. In human hepatic bile, which is generally dilute and markedly supersaturated with Ch, these vesicles may be the predominant form of Ch and L solubilization and transport [261]. If hepatic bile is extremely dilute, it is theoretically possible that no BS-L-Ch micelles may be present [268] all of the lipid content may be aggregated... 

The export of phospholipids and cholesterol can be simultaneous owing to the activity of various members of the ABC superfamily (see Table 18-2). The best-understood example of this phenomenon is in the formation of bile, an aqueous fluid containing phospholipids, cholesterol, and bile acids, which are derived from cholesterol. After export from liver cells, phospholipids, cholesterol, and bile acids form water-soluble micelles in the bile, which is delivered through ducts to the gallbladder, where it is stored and concentrated. In response to a fat-containing meal, bile is released into the small intestine to help emulsify dietary lipids and thus aid in their digestion and absorption into the body. As we shall see later, the alteration of biliary metabolism by drugs can be used to prevent heart attacks. 

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