Effect on bilirubin excretion of blocking the carboxyl sites of glucuronide conjugation by methylation.

Abstract

IN mammals the haem groups of haemoglobin are not re-utilized when red cells break down, but are converted to bilirubin (Fig. 1). This pigment is excreted into the bile as a diglucuronide. The reason why conjugation with glucuronic acid is necessary for the excretion of bilirubin, and the location of the glucuronyl residues on the bilirubin molecule, are not known with certainty. A partial or complete deficiency of the enzyme conjugating bilirubin (in the newborn infant, in Gunn rats and in patients with the Crigler–Najjar syndrome) is associated with a partial or complete block in biliary excretion of the pigment. This suggests that conjugation is a prerequisite for secretion, and is supported by the observation that Gunn rats can excrete injected bilirubin glucuronide1. Jirsa and Billing (unpublished) have found that both Gunn rats and normal rats excrete synthetic taurobilirubin, a derivative which is polar and water-soluble like the glucuronide.