Bile acid glucuronides excretion

In each form of cholestasis, atypical bile adds, such as monohydroxy bile acids, aUo-bile adds, 1- or 6-hydroxylated bile acids and their sulphated or glucuronidated derivatives, are found in the sermn and/or urine. In cholestasis, the increase in the neosynthesis of atypical bile adds that pass into the kidney can be seen as a compensatory mechanism which eliminates potentially hepatotoxic bile acids by renal clearance. The highest renal excretion quota is demonstrated by tetrahydroxy bile acids. 

The presence of bile alcohols in human urine was first demonstrated in 1981 by Karlaganis et al. [78]. Studying metabolic profiles of bile acids in urine, they found a number of bile alcohols in the steroid glucuronide fraction. The major compound was identified as 27-nor-5 6-cholestane-3a,7a,12a,24,25-pentol [78]. Excretion of this Cjf, bile alcohol as the major bile alcohol in urine from healthy and diseased humans was confirmed by Karlaganis et al. [79] and by Ludwig-Kohn et al. [94]. The latter authors also identified 5)8-cholestane-3a,7a,12a,25,26-pentol in human urine [94]. 

Vitamin D is absorbed in the lower portion of the intestine after uptake of the sterol by the mucosal tissue, and it is transferred to the lymph. Like vitamin A, vitamin D is esterified in the intestinal mucosa. Esterification occurs with a number of fatty acids, predominantly palmitate, but also stearate, linoleate, oleate, andmyronate. Again like vitamin A, vitamin D is stored in the liver in the form of the ester. Two other groups of vitamin D metabolites are also known excretory products (glucuronide and bile acid derivatives) and active forms (hydroxylated derivatives). A portion of vitamin D is excreted in the bile where it appears conjugated either to glucuronides or to tau-rocholic acid [10]. 

At normal levels of intake, most retinol is catabolized by oxidation to retinoic acid and excreted in the bile as retinoyl glucuronide. As the liver concentration or retinol rises above 70 LLmol/kg, there is microsomal cytochrome P -dependent oxidation, leading to a number of polar metabolites, which are excreted in the urine and bile. At high intakes this pathway becomes saturated, and excess retinol is toxic because there is no further capacity for its catabolism and excretion. 

Table XVIII shows that when phcnolphthalein glucuronide is administered intravenously to cats, about a tliird of the dose is excreted unchanged in the bile. However, when phenolphthalein, which has to be conjugated with glucuronic acid before excretion, is given, only about one-ninth of the dose appears in the bile. The low biliaiy excretion of phenolphthalein in the cat can be explained by the poor ability of this species to sjmtbesize glucuronides.

The uronic acid pathway is the source of glucuronic acid for conjugation of many endogenous and exogenous substances before excretion as glucuronides in urine and bile. 

The metabolites and metabolic pathway of a new anticonvulsant drug, sodium valproate, in rats were investigated using carbon-14 labeled sodium valproate. Most of the metabolites in urine and bile were a glucuronide conjugate of valproic acid. Free sodium valproate was as little as one-seventh of the total metabolites. In feces, only free sodium valproate was detected, and the possibility of enterohepatic circulation of sodium valproate was presumed. A part of dosed sodium valproate was excreted in expired air in the form of CO2. This degradative reaction took place in liter mitochondria and required CoA and oxygen. It was stimulated by ATP... 

The fate of chlordecone in humans involves uptake by the liver, enzymatic reduction to chlordecone alcohol, conjugation with glucuronic acid, partial conversion to unidentified polar forms, and excretion of these metabolites mainly as glucuronide conjugates into bile (Fariss et al. 1980 ... 

Male Wistar rats given single oral doses of 10, 50, or 250 mg/kg of1,4-dichlorobenzene (vehicle not given) excreted the majority of derived from 1,4-dichlorobenzene in the urine as either the sulfate conjugate (60%) or the glucuronide (30%). Bile contained 5 and 30% of the total radioactivity after the low and high doses, respectively. Only minor amounts of mercapturic acid were found (Hissink et al. 1997). 

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