Bile acid sulfates polarity

In phase 1 reactions, xenobiotics are generally converted to more polar, hydroxylated derivatives. In phase 2 reactions, these derivatives are conjugated with molecules such as glucuronic acid, sulfate, or glutathione. This renders them even more water-soluble, and they are eventually excreted in the urine or bile. 

A cytosolic sulfotransferase has been identified in rat liver and kidney which utilizes 3 -phosphoadenosine-5 -phosphosulfate (PAPS) and shows a greater rate of sulfation for glycolithocholate than lithocholate. In an assay with the enzyme preparation, PAPS, and conjugated bile acids, 3 unidentified products were formed from taurocholate suggesting multiple sulfation of more polar conjugated bile acids [64]. The enzyme from liver, proximal intestine or adrenals of hamster produced only glycochenodeoxycholate 7-sulfate. Comparable results with the enzyme from kidney will be discussed in Section VI.3. Hepatic enzyme from the female hamster shows 4-fold greater activity than that of the male [65]. 

Chemically, the bile acids are hydroxylated derivatives of cholanic acid, a tetracyclic steroid acid of 24 carbon atoms. The acids occur in nature largely as the water-soluble sodium salts of peptide conjugates of glycine and taurine. The free acids are liberated by saponification or specific enzyme hydrolysis. The chemistry of the bile acids has been reviewed in Chapter 1 of this volume (1). In view of their highly polar nature, special attention is called to the recent discovery of the cholic acid conjugates of ornithine (2, 3) and the 3a-sulfate esters of glycolithocholic and taurolithocholic acids (4). 

It originates mainly from bacterial 7a-dehydroxylation of chenode-oxycholic acid in the intestine, but can also be formed in the liver by an alternative pathway involving 26-hydroxylation of choles-terol[9]. Little is known about the significance of lithocholic acid in the pathogenesis of cholestasis in man. It has been claimed that the human liver is protected from lithocholic acid-hepatoxicity by the efficient sulfation of the 3a-hydroxy group[10], which increases the bile acids polarity. Sulfated bile acids are poorly absorbed from the intestine[11,12] and their renal clearance is relatively high[13]. Therefore, sulfation of lithocholic acid should promote its elimination from the body[14]. 

Bilirubin is nonpolar and would persist in cells (eg, bound to lipids) if not rendered water-soluble. Hepatocytes convert bilirubin to a polar form, which is readily excreted in the bile, by adding glucuronic acid molecules to it. This process is called conjugation and can employ polar molecules other than glucuronic acid (eg, sulfate). Many steroid hormones and drugs are also... 

About 20% of an oral dose of [ H] phylloquinone is excreted in the feces unchanged, suggesting that 80% is absorbed. A further 35% to 40% of the radioactivity is recovered in the feces as a variety of conjugates of polar metabolites formed by methyl oxidation of the side chain, followed by successive -oxidation, as well as reduction of the quinone ring to the quinol, to provide the site for conjugation with glucuronic acid, phosphate, or sulfate. About 75% of the conjugates are excreted in the bile and the remainder in the urine. In... 

PAHs are enzymatically converted in mammalian cells to polar reactive intermediates, capable of covalently binding to cellular macromolecules. This metabolism is complex, involving many steps and enzymes. Most of these intermediate species are converted through secondary metabolic processes in the liver to form inactive products (e.g., glucoronides, sulfates, glutathione conjugates). These are excreted in urine and bile and it is only those products that escape these secondary reactions that react with nucleic acids and proteins, and probably lead to carcinogenesis. 

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