Inhibition of human lymphocyte coproporphyrinogen oxidase activity by metals, bilirubin and haemin.

Coproporphyrinogen III oxidase activity in human lymphocytes was found to be inhibited by cadmium and mercury but not by lead. The organo-metal compounds tributyltin and methylmercury were effective inhibitors of this haem biosynthetic pathway enzyme. Haemin (the ultimate product of the pathway) and bilirubin (a product of haem catabolism) were also shown to be inhibitory. Kinetic studies performed under initial velocity conditions showed that bilirubin was a non-competitive inhibitor and that one bilirubin molecule was bound to both the enzyme and enzyme substrate complex. The analysis also showed haemin to be a non-competitive inhibitor in which two haemin molecules bind to the enzyme whereas the enzyme substrate complex accepts only one haemin molecule. The possible physiological significance of the inhibition of coproporphyrinogen III oxidase activity by haemin and bilirubin is discussed.