Conjugation of bilirubin

Bilirubin formed in peripheral tissues is transported to the hver by plasma albumin. The further metabolism of bihtubin occuts primarily in the hver. It can be divided into thtee processes (1) uptake of bilirubin by hver parenchymal cells, (2) conjugation of bilirubin with glucuronate in the endoplasmic reticulum, and (3) secretion of conjugated bilirubin into the bile. Each of these processes will be considered separately. 

Conjugation of Bilirubin With Glucuronic Acid Occurs in the Liver... 

Figure 32-14. Conjugation of bilirubin with glucuronic acid. The glucuronate donor, UDP-glucuronic acid, is formed from UDP-glucose as depicted. The UDP-glucuronosyl-transferase is also called bilirubin-UGT.

In most normal adult animals, conjugation of bilirubin with various sugars probably represents the major mechanism for its transformation (Fig. 1). The reaction products are eliminated from the organism by excretion into the bile. Glucuronyl transfer has been investigated in... 

With washed microsomal preparations from the liver of guinea pig, rat, rabbit, mouse, and cat, conjugation of bilirubin also occurred at appreciable rates in the absence of added bivalent cation (P3). With digitonin-activated preparations from rat liver, glycosyl transfer rates were, respectively, 16-33%, 0-38%, and 58-78% of the values found at nearsaturation of Mg + when UDP-glucuronic acid, UDP-xylose, or UDP-glucose were assayed (F3, HIO). The great variability of the rates could point to an artifact. 

Considering the large variety of glycosidic conjugates of bilirubin demonstrated in normal bile of man (F6, HIO), dog (F7), and rat (F7,... 

Isselbacher, K. J., and McCarthy, E. A., Studies on bilirubin sulphate and other nonglucuronide conjugates of bilirubin. J. Clin. Invest. 38, 645-651 (1939). 

T6. Thaler, M. M., Substrate-induced conjugation of bilirubin in genetically deficient newborn rats. Science 170, 555-556 (1970). 

Fig. 3. A possible mechanism for the conjugation of bilirubin with glucuronic acid (BIO).

In infants, even in the absence of disease, the concentration of bflirubin rises after birth because of the enhanced erythrocyte destruction. Its concentration peaks about die third to fifth day of hfe. Conjugation of bilirubin is relatively poor in the neonate as a result of immature liver function. 

Fig. 11. Formation of bilirubin-glutathione conjugates. This mechanism for conjugation of bilirubin and GSH was proposed by Odell et al. (01).

Jaundice may be a consequence of haemolysis, cholestasis or hepatocellular damage. The causes and features of these arc summarized in Figure. 3 and Table I. In addition there are inherited disorders of bilirubin metabolism. Gilbert s disease is the most common and causes a mild unconJugated hyperbilirubinaemia because of defective conjugation of bilirubin. 

Binding to GSTs Hepatic conjugation of Bilirubin to mono-and di-glucuronides by UDP glucuronyl transferase... 

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