Steroids bile acid

Steroidogenic type - steroids, bile acids, cholesterol, prostaglandin biosynthesis. 

A4 Nifedipine, ethylmorphine, warfarin, quinidine, taxol, ketoconazole, verapamil, erythromycin, diazepam Aflatoxin, 1-nitropyrene, benzo(a)pyrene 7,8-diol, 6 aminochrysene, estradiol, progesterone, testosterone, other steroids, bile acids Erythromycin, nifedipine [testosterone (6-/3)]... 

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). 

K. Miki, A. Masui, N. Kasai, M. Miyata, M. Shibakami, K. Takemoto, New Channel-Type Inclusion Compound of Steroidal Bile Acid Structure of a 1 1 Complex between Cholic Acid and Acetophenone , J. Am. Chem. Soc., 110, 6594 (1988)... 

Miki, K., Masui, A., Kasai, N., Miyata, M., Shibakami, M., and Takemoto, K., New channel-type inclusion compound of steroidal bile acid. Structure of a 1 1 complex between cholic acid and acetophenone, J.Am. Chem. Soc. 110, 6594-6596 (1988). 

In rats, OAT-K2, as OAT-Kl, was localized in the apical membrane of straight proximal tubule [52]. When transfected in cultured epithehal cells, it mediates not only the apical transport of methotrexate and folate but also that of taurocholate and prostaglandin E2. In cis-inhibition studies, steroids, bile acid analogs, and cardiac glycosides were shown to have a high affinity for OAT-K2, suggesting that it participates to the apical transport of hydrophobic anionic compounds in the kidney [52]. 

Steroids, bile acids, and similar compounds pose certain problems when they require to be derivatized for separation by GC. The hydroxyl groups in the respective structures differ greatly in their reaction rate, which will depend on their nature (whether they are primary, secondary, or tertiary) and also, to a certain extent, on their steric environment. 

Figure 26.2 Naturally-occurring steroidal bile acids involving cholic acid and its related derivatives.

Echchgadda, I., Song, C. S., Oh, T., Ahmed, M., De La Cruz, I. J., and Chatterjee, B. (2007) The xenobiotic-sensing nuclear receptors pregnane X receptor, constitutive androstane receptor, and orphan nuclear receptor hepatocyte nuclear factor 4alpha in the regulation of human steroid-/bile acid-sulfotransferase. Mol. Endocrinol. 21, 2099-2111. 

As noted earlier, bile acids were among the first steroids to be obtained in pure crystalline form. These compounds played an important role in the effort devoted to divining the structure of steroids. Bile acids as a result acquired a sizeable number of trivial names, most of which gave little information as to their chemical structure. One approach to systematic names is based on the hypothetical cholanoic acid 8-1 (Scheme 8). Bile acids are then named as derivatives of this structure using the mles used for other classes of steroids. Note the cis A-B ring fusion in this series. The systematic name for 8-2, lithocholic acid, is then simply 3a-hydroxy-5/3-cholanic acid. Chenodeoxycholic acid, 8-3, becomes 3a,7a-dihydroxy-5/3-cholanic acid. The predominant acid in bile, 8-3, is cholic acid itself, or, 3a,7a,12a-trihydroxy-5 )8-cholanic acid. 

Selenium was first used as dehydrogenation catalyst by Diels,127 when by this method he established cyclopenta[a]phenanthrene as the parent skeleton of steroids, bile acids, steroid hormones, and other natural products. Dehydrogenation by selenium requires the use of higher temperatures and is thus often accompanied by side reactions. 

Figure 8.1. A model of the transcriptional regulation of CYP3A expression by PXR. The PXR binds as a heterodimer with RXR to response elements in the promoter of CYP3A and other target genes. Binding of ligand to the PXR results in increased CYP3A enzyme activity, which in turn increases the hydroxylation of substrates such as steroids, bile acids, and drugs,...

Nature avoids micelles made of soaps because they first integrate into biomembranes and then degrade them. Steroidal bile acids are used instead for the dissolution of water-insoluble foodstuffs in water (see Sec. 3.5). 

Gdaniec, M. Milewska, M.J. Polonski, T. Enantioselec-tivc complexation of N-nitrosopiperidines by the crystal lattices of steroidal bile acids. Angew. Chem., Int. Ed. Engl. 1999, 38, 392-395. 

Lipids occur widely in nature. For examples, phospholipids are the main building blocks of biological membranes. Lipids exist in a variety of distinct forms, such as fatty acids, acylglycerols, phospholipids, sphingomyelins, glycosphingolipids, gangliosides, steroids, bile acids, prostaglandins, and leukotrienes. Some of lipids are structurally simple molecules, but others are complex molecules. Many are amphiphilic compounds. 

FAB and ESI have also proven useful for characterizing steroids, bile acids, and all types of eicosanoids. Although positive- and negative-ion modes have both been used, the latter provide better detection sensitivity and information content, owing to the presence of carboxylate functionality in these molecules. 

There are many pharmaceutical preparations and biological compounds containing carboxylic group, i.e., fatty acids, prostaglandins, steroids, bile acids, a-keto acids, and glucuronic acid. These compounds play important physiological roles to achieve homeostasis. 

Polar derivatives of cholesterol, such as keto and hydroxy steroids, bile acids, and ecdysteroids have all been extensively studied. 

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