PEDIATRICS Vol. 32 No. 1 July 1963, pp. 47-51
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STUDIES ON THE EFFECT OF NOVOBIOCIN ON GLUCURONYL TRANSFERASE

Howard Lokietz M.D.1, Robert M. Dowben M.D.2, and David Yi-Yung Hsia M.D.3

1 The Genetic Clinic, The Children's Memorial Hospital
2 The Department of Pediatrics, Northwestern University Medical School
3 The Department of Medicine, Northwestern University Medical School

Novobiocin has been found to be a potent inhibitor of glucuronyl transferase, the enzyme which catalyzes the conjugation of bilirubin. When 500 mg/kg was injected into newborn rats, enzyme activity in animals sacrificed 2 to 8 hours later was found to be less than half that observed in littermates who were injected with saline solution. This in vivo effect became less marked at 24 hours, when bilirubin levels were at their peak.

These findings were confirmed in in vitro systems using rat liver microsomes and o-aminophenol, p-nitrophenol, and 4-methylumbelliferone as substrates. The concentrations resulting in 50% inhibition averaged 1.5 x l0-4 M. Classic kinetic studies gave a value for Km of 1.08 x 10-4. Lineweaver-Burk plots and the near identity of Km and K1 show novobiocin to be a noncompetitive inhibitor.

In the past, neonatal hyperbilirubinemia has been attributed to either an immaturity or an overloading of the glucuronyl transferase system. The present study represents an example of jaundice in the newborn probably caused by an inhibitor of the enzyme system.

Submitted on March 22, 1962
Accepted on February 20, 1963