Bile acid glucuronides polarity

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 ... 

Most vitamin D is excreted in the bile less than 5% is excreted as water-soluble metabolites in urine. Some 2% to 3% of the vitamin D in bUe is cholecalciferol, calcidiol, and calcitriol, but most is a variety of polar metabolites and their glucuronide conjugates. In most tissues, the major pathway for inactivation of calcitriol is by way of 24-hydroxylation to calcitetrol, then onward oxidation byway of the 24-oxo-derivative, 23-hydroxylation, and oxidation to calcitroic acid (see Figure 3.3). In addition, a variety of hydroxylated and other polar metabolites have been identified in bile, and many of these onward oxidation products also undergo glucuronide conjugation in the liver (Reddy and Tserng, 1989). 

Retinoic acid from the intestinal mucosa is transported bound to serum albumin via the portal vein. Retinoic acid cannot be significantly reduced to retinal but is rapidly metabolized in tissue, such as Uver, to yield more polar catabohtes (e.g., 5,6-epoxyretinoic acid) and conjugates, such as retinoyl p-glucuronide, that are excreted. A small amount of retinoic acid undergoes enterohepatic circulation after intestinal hydrolysis of the glucuronide is excreted in the bile. 

The findings of Fidge et al. (1968) were consistent with earlier observations (Zachman and Olson, 1965 Zachman et al., 1966) that retinoic acid, injected into the portal vein, was rapidly metabolized and excreted in the bile. The labeled compounds found in bile consisted of a mixture of polar metabolites, most of which were more polar than free retinoic acid. One of the metabolites of retinoic acid in bile has been identified as retinoyl -glucuronide (Dunagin et al., 1965 Zile et al., 1980, 1982a Swanson et al., 1981). Other polar metabolites account for most of the radioactivity in bile after administration of labeled retinoic acid to rats (Zile et al., 1980, 1982a) one of these has been identified as a taurine conjugate of a retinoic acid metabolite (Skare et al., 1982). 

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. 

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