Metal inhibition of ferrochelatase.

Ferrochelatase activity was examined both in growing MEL cells and in in vitro assays of the purified enzyme to determine what effect a variety of divalent cations would have. Data obtained with the purified enzyme demonstrated that Mn2+ strongly inhibits the activity in a competitive fashion with respect to Fe2+ with a calculated Ki of 15 microM. Cadmium ion is also inhibitory (Ki: 50 microM), as is Hg2+ and arsenite, but Pb2+ is a poor inhibitor. All other metals tested had no effect. When these same metal ions were tested on differentiating MEL cells it was found that their ability to inhibit both heme formation and ferrochelatase activity mimicked their in vitro effect on purified ferrochelatase.