Bile acid glucuronides

Bile acid glucuronides may be hydrolyzed by -glucuronidase (EC 3.2.1.31) from bovine liver or the digestive juice of Helix pomatia (S41). The latter enzyme preparation also contains sulfatase activity (S41), but this is likely to be an aryl sulfatase which may not use bile acid sulfates as substrates. 

A7. Alme, B., and Sjdvall, J., Analysis of bile acid glucuronides in urine. Identification of 3a,6a,12a-trihydroxy-5 -cholanoic add.. Steroid Biochem. 13, 907-916 (1980). 

B. (2003) Peroxisome proliferator-activated receptor alpha induces hepatic expression of the human bile acid glucuronidating UDP-glucuronosyltransferase 2B4 enzyme. J. Biol. Chem. 278, 32852-32860. 

Barbier, O., Duran-Sandoval, D., Pineda-Torra, I., Kosykh, V., Fruchart, J. C., and Staels, B. (2003) Peroxisome proliferator-activated receptor alpha induces hepatic expression of the human bile acid glucuronidating UDP-glucuronosyltransferase 2B4 enzyme. J. Biol. Chem. 278, 32852-32860. 

Base peak in 3P-hydroxy-5-cholestanoate Characteristic of oxo-monohydroxy-C24 structure Feature of C-6 hydroxy bile acids Low intensity in bile acid glucuronides Prominent ion in THCA... 

The most common assay uses 3a-hydroxysteroid dehydrogenase to form the 3-keto bile acid that is trapped by, for example, hydrazine hydrate, causing the reaction to go to completion. The co-factor NAD is reduced stoichiometrically and can be measured by ultraviolet absorption or more commonly by fluorescence at an activation of 345 nm and emission of 450 nm. Use of this enzyme measures all bile acids with a 3a-hydroxyl but not cholesterol, which has a 3p-hydroxyl, and does not measure bile acids with a sulphate or glucuronide group conjugated to the 3a-hydroxyl. 

The OATP-C, also referred to as liver specific transporter 1 (LST-1) or OATP2, was cloned by number of groups (8,24,25) and was shown to be exclusively expressed in the basolateral membrane of the liver (25). As with OATP-A, OATP-C has broad substrate specificity and transports bile acids (13), sulfate and glucuronide conjugates (25), thyroid hormones (13), and peptides (16), and drugs such as pravastatin (24), methotrexate (26), and rifampin (27). Given its liver-specific expression and broad substrate... 

Glucuronidation is an important step in the elimination of many important endogenous substances from the body, including bilirubin, bile acids, steroid hormones, thyroid hormones, retinoic acids, and biogenic amines such as serotonin. Many of these compounds are also substrates for sulfonyltransferases (SULTs) (2). 

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. 

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