Cholesterol glucuronides

Bromothymol blue (6.0...7.6) acid lipids, cholesterol glucuronides and gangliosides [241] aryloxybutanolamine derivatives [242] norfenfluramine derivatives [243] ethylamphetamines [244] in volatile mineral oil hydrocarbons [245] phospholipids [91]... 

The blood and tissues of animals typically contain not only unesterified cholesterol (UC), but also cholesterol esters (CE). Most of the CE are formed from long-chain fatty acids such as palmitic acid, oleic acid, linoleic acid, or arachidonic acid, but small amounts of cholesterol sulfate (CS) and cholesterol glucuronide also are present. The aim of this chapter is to provide a brief overview of the biochemistry, physiology, and pathology of these esters as an introduction to the field of CE research. The primary focus will be on long-chain fatty acid esters because much more is known about them than about other CE. However, current knowledge of the biochemistry of CS will be reviewed as well. 

Zaks, A. and Dodds, D.R., Enzymatic glucuronidation of a novel cholesterol absorption inhibitor, Sch 58235. Appl. Biochem. Biotechnol., 1998, 73, 205. 

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. 

Appl. Catal. A General 2001, 221, 145-158. P. Reiss, D. A. Burnett, and A. Zaks, An enzymatic synthesis of glucuronides of azetidinone-based cholesterol absorption inhibitors, Bioorg. Med. Chem. 1999, 7, 2199-2202. 

Orally administered fluorescein is readily absorbed in the small intestine. By contrast fluorescein coupled to dilaurate cannot be absorbed unless the composite molecule is cleaved intra-duodenally by the pancreatic cholesterol esterase to form lauric acid and (absorbable) fluorescein. After its absorption, fluorescein is partly glucuronidated in the liver and then excreted in urine, predominantly as fluorescein diglucuronide. Thus, in pancreatic-insufficient... 

Bile alcohols are polyhydroxy C27 sterols that serve as intermediates in the biosjmthesis of cholic acid and chenodeoxycholic acid from cholesterol (1, 2). Recently several studies have shown that increased amounts of bile alcohols namely 27-nor-5p-cholestane-3a,7a,12a,24, 25-pentol and 5P-cholestane-3a, 7a,12a,25,26-pentol are excreted (as glucuronides in urine of patients with liver diseases such as primary biliary cirrhosis (3), liver cirrhosis (4, 5) and a-antitrypsin deficiency (6). Ichimiya et. al., described the occurrence of 5P-cholestane-3a,7a,12a,26,27-pentol (5P-cyprinol) and 5P-cholestane-3a,7a,... 

In summary, these studies demonstrated that in CTX the impaired synthesis of bile acids is due to a defect in the biosynthetic pathway involving the oxidation of the cholesterol side-chain. As a consequence of the inefficient side-chain oxidation, increased 23, 24 and 25-hydroxylation of bile acid precursors occurs with the consequent marked increase in bile alcohol glucuronides secretions in bile, urine, plasma and feces (free bile alcohols). These compounds were isolated, synthesized and fully characterized by various spectroscopic methods. In addition, their absolute stereochemistiy determined by Lanthanide-Induced Circular Dichroism (CD) and Sharpless Asymmetric Dihydroxylation studies. Further studies demonstrated that (CTX) patients transform cholesterol into bile acids predominantly via the 25-hydroxylation pathway. This pathway involves the 25-hydroxylation of 5P-cholestane-3a,7a, 12a-triol to give 5P-cholestane-5P-cholestane-3a,7a,12a,25- tetrol followed by stereospecific 24S-hydroxylation to yield 5P-cholestane-3a,7a,12a,24S,25-pentol which in turn was converted to cholic acid. 

Figure 9 The pancreolauryl test allows an indirect assessing of exocrine pancreatic function. Orally administered fluorescein dilaurate is hydrolyzed by carboxylester lipase (identical to cholesterol esterase) liberating lauric acid and free, water-soluble fluorescein. The latter is readily absorbed in the small intestine, partly conjugated in the liver, and excreted in urine mainly as fluorescein glucuronide. By measuring the concentration of fluorescein in the urine over a period of, for instance, 10 hours, the total quantity of this dye is determined. (From Ref. 52.)...

Estrogen Estrogen-sullate Cholesterol Cholesterol-sulfate Androgen Androgen-glucuronide... 

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