Bile acids, molecular structure

Chadwick, Y.S., et al. 1979. Effect of molecular structure on bile acid-induced alterations in absorptive function, permeability and morphology in the perfused rabbit colon. J Lab Clin Med Sci 94 661. 

CHARACTERISTIC STRUCTURES OF BILE ACID DERIVATIVES 2.1 Unique Molecular Structures... 

Bile acids can be modified to many derivatives due to their unique molecular structures, as listed in Table 1. First, we can convert the functional groups at the side-chains from carboxylic acid to amide, alcohol, ester, and so on. Second, we can change the length of the side-chains by decreasing or increasing their methylene number. Third, we can regulate the direction of the hydroxyl groups of the skeletons at the axial or equatorial positions. 

We have researched the inclusion abilities of bile acid derivatives by using more than one hundred organic compounds as guest candidates. The inclusion phenomena vary from one case to another, indicating that subtle changes in molecular structures induce alteration in their molecular assemblies. In fact, X-ray diffraction studies prove that the steroidal hosts form various assemblies such as monolayers, bilayers, helical tubes, and so on, as shown in Figure 2. Therefore, systematic investigation of inclusion crystals of bile acid derivatives is expected to reveal a relationship between their molecular structures, assemblies and inclusion behavior. 

Fats and fat-like compounds of varying chemical structures are classified as lipids. They have a low molecular weight and are insoluble in water. The original substance in fat biosynthesis is acetyl-CoA (so-called activated acetic acid). On the basis of chemical criteria, they may be divided into simple lipids (glycerides, cholesterol, cholesterol esters, bile acids) and complex lipids, (s. tab. 3.7)... 

I thank my coworkers, who are mentioned in the references, for the work on bile-acid-derived molecular receptors carried out at Bangalore. Financial support by the Department of Science and Technology and by the Department of Biotechnology is gratefully acknowledged. I also thank Mr Koushik Das Sarma for drawing all the structures for this article. 

Active transport mechanisms for the intestinal absorption of amino acids, oligopeptides, monosaccharides, monocarboxylic acids, phosphate, bile acids, and a number of vitamins have been identified and the review by Tsuji and Tamai provides an excellent summary of those mechanisms. The potential use of intestinal peptide and hepatic bile acid carriers to enhance drug absorption also has been reviewed. Structural and molecular modeling studies have postulated molecular structural features necessary for substrate recognition by the intestinal peptide carrier and the bile acid carrier. ... 

Schematic models for the expanded structure of bile acid-phosphatidylcholine mixed micelles are shown in Fig. 2B. The original model was proposed by Small in 1967 (S36). In this model the mixed micelle consisted of a phospholipid bilayer disk surrounded on its perimeter by bile acid molecules, which were oriented with their hydrophilic surhices in contact with aqueous solvent and their hydrophobic sur ces interacting with the hydrocarbon chains of the phosphohpid molecules. This model has recently been revised, based on further studies of mixed micelles using quasi-elastic light scattering spectroscopy (M20). In a new model for the molecular structure of bile acid-phospholipid mixed micelles. Mazer et al. (M20) propose a mixed disk, in which bile acids are found not only on the perimeter of phospholipid bilayers, but also incorporated within their interior in high concentrations (Fig. 2B). The size of these mixed micelles was estimated to be as high as 200 to 400 A in radius in some solutions, and disk-shaped particles in this size range were observed by transmission electron microscopy (M20). Micellar aggregates similar in size and structure to those found in model bile solutions have been demonstrated in dog bile (M22).

Structure-Activity Reiationships for ASBT. The studies with endogenous bile acids have led to physiological understanding of the function of bile acids and the enterohepatic circulation. The search for a deeper understanding of the molecular mechanism behind the affinity and recognition of molecules by the bile acids carriers in both ileum and liver has led researchers to modify bile acids and study the carrier affinity of these compounds. These modifications typically entail either the substitution of the hydroxyl groups at the 3,7, or 12 positions by other functionalities or the... 

The common bile acids and salts possess a characteristic molecular structure shown schematically for sodium cholate in Fig. 1 [7]. In contrast to the all irons arrangement of the alicyclic ring systems in alio bile salts, a crucial feature of the... 

See also Steroids, Molecular Structures and Properties of Lipids (from Chapter 10), Bile Acids, Steroid Hormone Synthesis... 

In a structure activity investigation, the following structural elements necessary for the molecular recognition of a bile acid by the ileal Na /bile acid transport system were identified [21,22] ... 

Maitra. U. Bag. B.G. Rao. P. Powell. D. Bile acids in asymmetric synthesis. 5. Asymmetric synthesis of steroidal Troger s base analogs. X-ray molecular structure of methyl 3a, 12a- 6H, 12H-5.1 I -methanodibenzo[b,f][l,5]diazo-cine-2,8-bisacetoxy -5P-cholan-24-oate. J. Chem. Soc., Perkin Trans. 1 1995, 2049-2507. 

The molecular arrangement of the bile acid-lipolytic product micelle is unknown but is probably similar to that of the bile acid-lecithin micelle, the structure of which, based on nuclear magnetic resonance studies, is a cylindrical bimolecular leaflet of lecithin molecules coated on the sides by bile acid molecules, their hydrophobic backs apposed to the paraffin chains of the phosphatide (65). All of the molecular species of the micelle are considered to be in rapid exchange with those of other micelles, as well as the concentration of molecularly dispersed lipolytic products and bile acids (at their CMC) in the bulk phase surrounding the micelles. Benzene molecules exchange rapidly between bile acid-monoglyceride micelles, a mean micellar... 

Bile acid metabolism in conventional animals is the activity of a balanced ecological system composed of the host, the associated intestinal microflora, and the diet. The host contributes the bile acids themselves and serves to maintain the homeostasis of the gastrointestinal tract. The intestinal microflora alters the molecular structure of the bile acids which it comes into contact with and also profoundly alters the physiological and, to a degree, the anatomical features of the host. The diet contributes the nutrition for both the host and the intestinal microflora and can cause marked changes in the flora s activity toward the bile acids in vivo (52). In addition, the amount of dietary sterols may cause the host to change its absorption and/or catabolism of cholesterol to bile acid and thus the rate of bile acid excretion (53). 

Amphiphilic molecules contain a polar and an apolar part. As a result, such molecules have an ambiguous (amphi) affinity (philos) for water. The apolar parts behave hydrophobically the water molecules tend to escape from contact with these parts. The polar parts are hydrophilic. They interact favorably with water. The consequence of the amphiphilic character is that the molecules are preferably located at interfaces with water, where the polar parts are exposed to the aqueous phase and the apolar parts to the nonaqueous phase. Low-molecular-weight, amphiphilic compounds are often called surfactants. Well-known examples of surfactants are the classical soaps (single-chain fatty acids), phospholipids, cholesterol, bile acids, lung surfactant, and so on. In Figure 7.1, the chemical structures showing the polar and apolar parts of some of these surfactants are given. Monolayers may also be formed by polymers, polyelectrolytes, and proteins that contain polar and apolar parts. 

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