Bile conjugates

Mammalian bile contains sodium salts of conjugated bile acids, e.g. glycocholic acid and taurocholic acid, in which cholic acid is combined (amide linkage) with glycine and taurine respectively. 

Only the small amounts of T and T that are free in the circulation can be metabolized. The main route is deiodination of T to T and i-T, and from these to other inactive thyronines (21). Most of the Hberated iodide is reabsorbed in the kidney. Another route is the formation of glucuronide and sulfate conjugates at the 4 -OH in the Hver. These are then secreted in the bile and excreted in the feces as free phenols after hydrolysis in the lower gut. 

Bile acids, which exist mainly as bile salts, are polar carboxylic acid derivatives of cholesterol that are important in the digestion of food, especially the solubilization of ingested fats. The Na and salts of glycocholic acid and tauro-cholic acid are the principal bile salts (Ligure 25.41). Glycocholate and tauro-cholate are conjugates of cholic acid with glycine and taurine, respectively. 

FIGURE 25.41 Cholic acid, a bile salt, is synthesized from cholesterol via 7o -hydroxy-cholesterol. Conjugation with taurine or glycine produces taurocholic acid and glycocholic acid, respectively. Taurocholate and glycocholate are freely water-soluble and are highly effective detergents. 

Because they contain both nonpolar and polar domains, these bile salt conjugates are highly effective as detergents. These substances are made in the liver, stored in the gallbladder, and secreted as needed into the intestines. 

MRP1 (ABCC1) Glucuronides and sulfate conjugates of steroid hormones and bile salts, colchicine, doxorubicin, daunorubicin, epirubicin, folate, irinotecan, methotrexate, pacitaxel, vinblastine, vincristine, and others... 

MRP2 (ABCC2) LTC4, bilirubin-glucuronide, estradiol 17 3-glucuronide, dianionic bile salts, anionic conjugates, glutathione disulfide, and others... 

Diclofenac is an exceedingly potent COX inhibitor slightly more efficacious against COX-2 than COX-1. Its absorption from the gastrointestinal tract varies according to the type of pharmaceutical formulation used. The oral bioavailability is only 30-80% due to a first-pass effect. Diclofenac is rapidly metabolised (hydroxylation and conjugation) and has a plasma half-life of 1.5 h. The metabolites are excreted renally and via the bile. 

Enterohepatic circulation can lead to toxic effects. For example, the drug chloramphenicol is metabolized to a conjugate that is excreted in bile by the rat. Once in the gut, the conjugate is broken down to release a phase 1 metabolite that undergoes further metabolism to yield toxic products. When these are reabsorbed, they can cause toxicity. The rabbit, by contrast, excretes chloramphenicol conjugates in urine, and there are no toxic effects at the dose rates in question. 

Bile acid conjugates la 376 Bile acid methyl esters lb 446,448 Binding agent, influence on staining la 123 S-Bioallethrine la 359... 

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. 

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