Bile acids chemical structures

The mechanistic basis of the anti-neoplastic activity of UDCA and the explanation for the significant difference in bioactivity of UDCA compared with DCA despite marked similarity in chemical structure remain unresolved. UDCA administration in healthy volunteers and colorectal adenoma patients has been demonstrated to decrease the proportion of DCA in aqueous phase stool. Therefore, one possible mechanism of the chemopreventative activity of UDCA is reduction of mucosal secondary bile acid exposure. Consistent with this idea, UDCA administration has been demonstrated to reduce the incidence of K-ras mutations and decrease Cox-2 expression in AOM-induced tumors, which is the opposite of the reported effects of DCA in the same model. However, it is clear that exogenous administration of UDCA has direct anti-neoplastic activity on human CRC cells in vitro, either alone or in combination with DCA, including anti-proliferative and anti-apoptotic effects, as well as induction of cell senescence. " ... 

Fig. 5.4.1 Chemical structures of bile acids (BAs) (reprinted from [2]). CA Cholic acid, CDCA chenodeoxycholic acid,...

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]. 

WIELAND, HEINRICH O. (1877-1957). A German chemist who won the Nobel prize for chemistry in 1927. His research included work on bile acids, organic radicals, nitrogen compounds, toxic substances, and chemical oxidation, as well as the discovery of the structure of cholesterol. He received his Ph.D. from the University of Munich. 

Several prominent types of host molecule, such as the steroidal bile acids and the cyclodextrins, are chiral natural products that are available as pure enantiomers. Chemical modification of these parent compounds provides an easy route to the preparation of large numbers of further homochiral substances. Since all these materials are present as one pure enantiomer, it automatically follows that their crystalline inclusion compounds must have chiral lattice structures. It is not currently possible to investigate racemic versions of these compounds, but the examples discussed previously in this chapter indicate that very different behaviour could result. 

The chemical modification of xenobiotics in the body is called biotransformation, metabolism, or metabolic clearance. Enzymes involved in metabolism are either membrane bound (e.g., endoplasmic reticulum and mitochondria) or freely soluble within the cytosol. Because these metabolic enzymes are not particularly substrate specific, they can metabolize compounds with fairly diverse chemical structures, including some endogenous compounds such as steroids, bile acids, and heme (endobiotics). 

There are many endogenous substrates, of widely different chemical structure, that are metabolized through oxidative, peroxidative, and reductive changes introduced by P450 enzymes. These include saturated and unsaturated fatty acids, eicosanoids, sterols and steroids, bile acids, vitamin D derivatives, retinoids, and uroporphyrinogens (Tables 9.4 and 9.5). 

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. 

The tertiary bile acids are formed in the liver as well as in the gut. (s. fig. 3.3) Intestinally absorbed lithocholic acid is enzymatically converted to sulpholitho-cholic acid in the liver. Ketolithocholic acid is transformed to (hypercholeretic) ursodeoxycholic acid in both the intestine and the liver. When passing through the canaliculi, UDC is partly reabsorbed by epithelial cells and returned to the liver via the blood circulation (= cholehepatic shunt). (41) The latter is chemically and structurally identical to chenodeoxycholic acid, of which it is deemed to be the 7P-epimer ... 

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)... 

Shefer, S., Salen, G., Cheng, F. W., Dayal, B., Batta, A.K., Tint, G.S., Bose, A.K.. and Pramanik, B.N. (1982). Chemical Ionization-Mass Spectrometric Approach to Structure Determination of an Intermediate in Bile Acid Biosyndiesis. Anal. Biochem 121 23-30. 

Fig. 1. Chemical structures of SP-cholestane (A), Sp-cholan-24-oic acid (B), and bile acids found in human gallbladder bile (C-G).

Bile acids contain hydroxyl groups, which are usually substituted at positions, C-3, C-7, or C-12 of the steroid nucleus. The three major bile acids found in man are 3a,7a,12a-trihydroxy-5P-cholan-24-oic acid 3a,7a-dihydroxy-5p-cholan-24-oic add and 3a,12a-dihydroxy-5p-cholan-24-oic acid. Because of the complexities of steroid nomenclature, bile acids are nearly always referred to by trivial names. 11108, the three major human bile acids are named cholic acid, chenodeoxycholic acid, and deoxycholic acid, respectively, and their chemical structures are shown in Fig. 1. Human bile does, however, contain small amounts of other bile acids, such as lithocholic acid (3a-hydroxy-5P-cholan-24-oic add) and ursodeoxycholic add (3a,7p-dihydroxy-5p-cholan-24-oic acid) (see Fig. 1). 

There is a wide variety in the types of bile acids found in different animal species. Some species have unique bile acids, such as a-muricholic acid (3a,6p,7a-trihydroxy-5p-cholan-24-oic add) and -muridiolic add (3a,6, 7 -trihydroxy- -cholan 24-oic acid) in rats and mice, and hyodeoxycholic acid (3a,6a-dihydroxy-Sp-cholan>24-oic acid) in pigs. Haslewood (H9) has studied the distribution of bile acids in the animal kingdom and has suggested that the C-24 adds, which are common to most advanced animal forms, can be regarded as the present endpoints in the evolution of the chemical structure of bile adds. 

A chemical, genetic, and structural analysis of the nuclear bile acid receptor FXR. Molecules and cells, 11, 1079-1092. 

Cholesterol is primarily restricted to eukaryotic cells where it plays a number of roles. Undoubtedly, the most primitive function is as a structural component of membranes. Its metabolism to bile acids and the steroid hormones is relatively recent in the evolutionary sense. In this chapter, the pathway of cholesterol biosynthesis will be divided into segments which correspond to the chemical and biochemical divisions of this biosynthetic route. The initial part of the pathway is the 3-step conversion of acetyl-CoA to 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). The next is the reduction of this molecule to mevalonate, considered to be the rate-controlling step in the biosynthesis of polyisoprenoids. From thence, a series of phosphorylation reactions both activate and decarboxylate mevalonate to isopen tenyl pyrophosphate, the true isoprenoid precursor. After a rearrangement to the allylic pyrophosphate, dimethylallyl pyrophosphate, a sequence of l -4 con-... 

This chapter reviews the natural distribution, the chemical structure, and the metabolism of bile alcohols and primitive bile acids. 

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