Bilirubin Glucuronyl transferase

P5. Potrepka, R. F., and Spratt, J. L., A study on the enz3rmatic mechanism of guinea-pig hepatic-microsomal bilirubin glucuronyl transferase. Eur. J. Biochem. 29, 433-439 (1972). 

S8) to be located in the microsome fraction of the liver. The neonatal development of this conjugating system has been studied by Brown et al. (B17) in the guinea pig. They were unable to detect the presence of bilirubin glucuronyl transferase in liver microsomes from fetal and newborn animals and, using o-aminophenol as a glucuronyl acceptor, were... 

The fact that jaundice was noticeably absent in adolescents treated in a prophylactic manner with isoniazid, despite the occurrence of abnormal SGPT values, prompted Cohen and McNamara to investigate the effects of isoniazid on bilirubin metabolism (3 ) using rats as an experimental model. They found that hepatic bilirubin glucuronyl-transferase activity was enhanced in the animals receiving the drug. Such enhanced activity could account for the absence of hyperbilirubinaemia in subjects with biochemical evidence of hepatic dysfunction whilst receiving isoniazid. 

Bl. Bakken, A. F., Effects of unconjugated bilirubin on bilirubin-UDP-glucuronyl transferase activity in liver of newborn rats. Pediat. Res. 3, 205-209 (1969). 

B17. Black, M., Billing, B. H., and Heirwegh, K. P. M., Determination of bilirubin UDP-glucuronyl transferase activity in needle-biopsy specimens of human liver. Clin. Chim. Ada 29, 27-35 (1970). 

M5 Menken, M., Barrett, P. V. D., and Berlin, N. I., Assay of hepatic glucuronyl transferase activity using ( C) bilirubin as substrate. Clin. Chim. Acta 14, 777-785 (1966). 

Odifevre, M., and Luzeau, R., Measurement of the activity of bilirubin UDP-glucuronyl transferase. Application to needle biopsy specimens. Rev. Eur. Etud. Clin. Biol. 16, 84-85 (1971). 

It has now been established that in common with many other glu-curonides, bilirubin glucuronide can be synthesized in the adult rat, rabbit, mouse, and guinea pig liver by the enzymatic transfer of glucuronic acid from uridine diphosphate glucuronic acid to an acceptor substance, namely, bilirubin (Fig. 3) (B17, G5, L3, L5, S8). The transferring enzyme (glucuronyl transferase) has been shown by Schmid et al. 

Subsequent studies have shown (e.g. 5,6, Table I) that the liver of newborns is indeed deficient in enzymes needed not only for drug metabolism but also for the elimination of natural products. For example, because of the lack of UDP-glucuronyl transferase resulting in the inability to dispose of bilirubin, the newborn is at risk for brain damage by kernicterus. That PEP carboxykinase, the key catalyst of gluconeogenesis de novo is absent at 7 months and still at low titers 3 days after birth (Table I), probably contributes to the fact that transient hypoglycemia (which can also cause brain damage) represents a hazard to full term as well as premature infants. The immaturity of the hepatic enzyme composition imposes limitations on the choice of nutrients used to supplement or re-... 

Bilirubin-UDP-glucuronyltransferase is one member of a family of glucuronyl transferases that participate in the metabolism of xenobi-otics (foreign compounds) by increasing their... 

Elevation of bilirubin commonly occurs in newborns. Sometimes this is not due to a deficiency in glucuronyl transferase but to blood group antigen-antibody incompatibilities which result in excess red cell destruction. Here, too, there is a rise in unconjugated bilirubin. Phototherapy and blood transfusion may both be helpful here. 

Indinavir has been compared with abacavir in a randomized equivalence trial in 562 patients who were also taking lamivudine and zidovudine (10). The only significant difference in adverse effects was that there was hyperbilirubinemia in 8% of those taking indinavir and 2% of those taking abacavir. It has been postulated that indinavir-induced hyperbilirubinemia is due to inhibition of bilirubin UDP glucuronyl transferase activity, since it is more common in individuals with Gilbert s syndrome (11). 

As adult cats have a relative deficiency in hepatic microsomal glucuronyl transferase activity, glucuronide conjugates of drugs and endogenous substances (such as bilirubin and steroidal substances) are slowly synthesized in... 

An inspiring, and likely the first, example for the therapeutic application of enzyme induction to affect the metabolic fate of an endogenous substance has recently been reported by Yaffe and his associates (71) phenobarbital treatment has been used to prevent hyperbilirubinemia by inducing the glucuronyl transferase, enhanced glucuronide formation enabled increased bilirubin excretion and resulted in decreased serum bilirubin concentration. 

Novobiocin has been associated with hyperbilirubinemia in the newborn (S46), and it has been shown to depress the excretion of BSP (B21a) and indocyanine green (H4, H5) as well as the maximal excretion rate for bilirubin (A3). Novobiocin also inhibits the excretion of bilirubin by liver slices (H5). Novobiocin was found to inhibit the glucuronyl transferase (H4), but this could be secondary to an accumulation of the conjugated bilirubin after inhibition of the excretory mechanism. Novobiocin, in contrast to other agents, also inhibits hepatic uptake of dyes and this may be its main effect (B21a). 

---