Bilirubin diglucuronide formation

A) a decrease in the rate of formation of bilirubin diglucuronides in the liver... 

Formation of bilirubin diglucuronide. Glucuronidation occurs in two steps via formation of monoglucuronide. Mono-and diglucuronides are more water-soluble and less lipophilic than bilirubin. Conversion of bilirubin to water-soluble products is obligatory for excretion of bilirubin from hepatocytes. M, Methyl V, vinyl UPD-GA, UDP-glucuronic acid. 

Fig. 30.5. Formation of bilirubin diglucuronide. A glycosidic bond is formed between the anomeric hydroxyl of glucuronate and the carboxylate groups of bilirubin. The addition of the hydrophilic carbohydrate group, and the negatively charged carboxyl group of the glucuronate, increases the water solubility of the conjugated bilirubin and allows the otherwise insoluble bihrubin to be excreted in the urine or bile.

H4. Halac, E., DiPlazza, M., and Detwiler, P., The formation of bilirubin mono- and diglucuronide by rat liver microsomal fractions. Biockim. Biophys. Acta 279, 544-553 (1972). 

Figure 9-8. Pathway for metabolism of heme and excretion as bilirubin. Heme degradation begins with heme oxygenase, which catalyzes a complex set of reactions that simultaneously open the protoporphyrin ring structure and release iron in the ferric (Fe ) state. This is the only physiologic reaction that makes endogenous CO in the body a portion of the small amounts made is expired via the lungs. The structure of the main form of bilirubin is shown. Symbols for the side groups indicate M, methyl V, vinyl P, propyl. Formation of the diglucuronide is catalyzed by bilirubin uridine diphosphate (UDP) glucuronyltransferase. RE, reticuloendothelial.

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