Glucuronic acid bilirubin conjugates

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

Bilirubin is nonpolar and would persist in cells (eg, bound to lipids) if not rendered water-soluble. Hepatocytes convert bilirubin to a polar form, which is readily excreted in the bile, by adding glucuronic acid molecules to it. This process is called conjugation and can employ polar molecules other than glucuronic acid (eg, sulfate). Many steroid hormones and drugs are also... 

Figure 32-13. Structure of bilirubin diglucuronide (conjugated, "direct-reacting" bilirubin). Glucuronic acid is attached via ester linkage to the two propionic acid groups of bilirubin to form an acylglucuronide.

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 the hver, bilirubin is made water-soluble by conjugation with two molecules of glucuronic acid and is secreted into the bile. The action of bacterial enzymes in the gut produces urobihnogen and urobihn, which are excreted in the feces and urine. 

Bilirubin is the waste product derived from haem catabolism. In order to be eliminated from the body, mainly via the gut, bilirubin must be processed through the liver (see Section 6.4). Bilirubin is, however, insoluble in water, so to reach the liver from the spleen where a substantial amount of red cell destruction occurs, bilirubin must first be bound to albumin. As blood perfuses the liver, bilirubin is transported into the hepatocyte where it is conjugated with glucuronic acid prior to excretion. 

As bilirubin can be converted in vitro into mono- and diconjugates of glucuronic acid (H4, R9, S6, SIO) and of xylose (F5), it is useful to distinguish the bilirubin conjugation rate (BCR) from the group trans-... 

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. 

In the procedure of Wong (W12) bilirubin is incubated enzymatically with [U- C]UDP-glucuronic acid of known specific activity. The derived azo pigments are transferred quantitatively to a thin-layer plate and are separated. The spot of conjugated azo pigment is eluted and counted. With other radioactive UDP-sugars, extension of the procedure to the corresponding transfer processes is obvious. 

F5. Fevery, J., Leroy, P., Van De Vijver, M., and Heirwegh, K. P. M., Structures of bilirubin conjugates synthesized in vitro from bilirubin and uridine diphosphate glucuronic acid, uridine diphosphate glucose or uridine diphosphate xylose by preparations from rat liver. Biochem. J. 129, 635-644 (1972). 

Schmid, R., and Lester, R., Implication of conjugation of endogenous compounds—Bilirubin. In Glucuronic Acid. Free and Combined. Chemistry, Biochemistry, Pharmacology, and Medicine (G. J. Dutton, ed.), pp. 493-506. Academic Press, New York, 1966. 

Failure to conjugate bilirubin to glucuronic acid causes accumulation of bilirubin in the unconjugated form in the blood. 

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

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