Bile acid conjugates structures

The taurine residue can also be found as an amide derivative of the 26-carboxylic acid function in the 3p,5a,6p,15a-polyhydroxylated steroids 328 and 329, which were obtained from the starfish Myxoderma platyacanthum [245]. The structures of both compounds were determined from spectral data and chemical correlations. The bile of the sunfish Mola mola has been shown to contain a new bile acid conjugated with taurine (330) together with sodium taurocholate. Compound 330 was identified as sodium 2-[3a,7a, 11 a-trihydroxy-24-oxo-5P-cholan-24-yl]amino]ethane-sulfonate on the basis of its physicochemical data and chemical transformations [246]. 

The liver, and also bacteria in the small and large intestine, can cause other structural modifications to bile acids as they undergo their entero-hepatic cycle. The formation of sulfate esters, already mentioned with respect to lithocholate in Section 4.2.1, is carried out primarily in the liver in man by a sulfotransferase (Lll). Other bile acids can also be sulfoconjugated to a small extent, mainly at the 3a-hydroxyl position. Bacteria, which have been isolated anaerobically from human feces, are known to possess bile acid sulfatase activity, which removes the 3a-sul te group of chenodeoxycholic and cholic acids (H24). The action of this bacterial enzyme probably explains why only trace amounts of sul ted bile acids, which are poorly absorbed in the intestine, are detected in the feces (12). Another type of bile acid conjugate, which has been identified in the urine of healthy subjects and patients with hepatobiliary disease, is the glucuronide (A7, S41). Both the liver and extrahepatic tissues, such as the kidney and small intestinal mucosa, are capable of glucuronidation of bile acids in man (M14). 

Figure 7 Structural formulas of bile acid conjugate with (a) chlorambcil and (b) NBD-oxalylpropylpeptide. (Adapted from Ref. 22.)... 

Figure 8 Influence of linker structure in HMG-CoA reductase inhibitor-bile acid prodrugs on the biliary secretion profile. The bile acid conjugates of the HMG-CoA reductase inhibitor HR 780 (1 mM) dissolved in 10 mM Tris/Hepes buffer (pH 7.4)/ 300mM mannitol/5% ethanol were injected as bolus into a mesenteric vein of anesthetized rats. After cannulation of the common bile duct, bile was fractionated and analyzed for the prodrugs or metabolites by thin-layer chromatography. (Adapted from Ref. 27.)...

Some structures of bile acid conjugates found in urine or plasma of a child with neonatal hepatitis of unknown etiology. 

FI GURE 4.3 Structures of allocholic acid (petromyzonol sulfate is identical apart from replacement of the carboxyl group with sulfate), taurine-conjugated bile acid, and geosmin. 

Mass spectrometry has become an indispensable method for the analysis of bile acids by virtue of its power to identify, assign structure and quantify free or conjugated bile acids, either pure or in mixtures. It is useful not only to study the metabolism of bile acids but also for the detection and diagnosis of metabolic diseases. Indeed, numerous metabolic diseases resulting from an alteration of the conversion of cholesterol to bile acids have been described, including peroxisomal disorders resulting in a block of (3-oxidation of the lateral chain and other enzyme deficiencies interfering with the biochemistry of the side chain or the steroid nucleus. 

These substrate molecules exhibit a wide variety of chemical structures. Some ABC proteins facilitate the transport of inorganic ions, whereas others pump various organic compounds, including lipids, bile acids, glutathione and glucuronide conjugates, or even short peptides. Most ABC family proteins utilize the energy of ATP hydrolysis for this transport activity (active transporters), but some ABC transporters form specific membrane channels. 

Bile salts with a steroid structure appear to be confined to vertebrates (76). In some evolutionarily more primitive vertebrates, the major bile salts are sulfate esters of polyhydroxy C27- and C26-steroids and/or taurine-conjugated C27-steroid acids. In other primitive vertebrates, C24 bile acids, usually cholic acid and/or allocholic acid, or mixtures of primitive bile salts (bile alcohols and C27 bile acids) and modern bile salts (C24 bile acids) occur. Most of the work concerning the structure and occurrence of primitive bile salts has been carried out in the laboratories of G. A. D. Haslewood and T. Kazuno, and Haslewood and collaborators have accumu-... 

Steroids and bile acids. The third major class of lipids is steroids. The structure of steroids is based on the cyclopentanoperhydrophenanthrene moiety (see Figure 12.5). Steroids exist in free form or as a conjugate of various molecules such as fatty acids, sulfuric acid, glucorinic acids, sugars, and amino acids. The most abundant steroid in the human body is cholesterol, which serves as a membrane component. It also acts as a precursor for the synthesis of other steroid hormones. Other known members of the steroid family are bile acids they are also derivative of cholesterol. 

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