A possible role of copper in the regulation of heme biosynthesis through ferrochelatase.
Experiments have been performed which show that it is possible to regulate heme biosynthesis by regulating ferrochelatase activity. Treatment of rats with the transition metals, Co-++ and Mn-+-+,  has been shown to inhibit ferrochelatase activity and to produce a dose-dependent decrease in hepatic cytochrome P-450 content. Unlike other transition metals, copper stimulated ferrochelatase activity and there was an interaction between Cu-+-+ and Fe-+-+ in the system such that the Km of Fe-+-+ was dependent on the concentration of copper. After solubilizing and dialyzing hepatic mitochondrial preparations, ferrochelatase activity was lost and could be restored by the addition of copper. In addition, copper, but not iron, reversed the inhibition of ferrochelatase activity produced by Pb-+-+ or Co-+-+. This study suggest that cytochrome P-450 content may be decreased during copper deficiency due to a decrease in ferrochelatase activity and a subsequent defect in heme biosynthesis. The synthesis of other hemoproteins may also be affected by copper deficiency. For example, it is well known that copper deficiency can lead to anemias (Lee et al., 1968) which might be explained by an intracellular defect in heme biosynthesis at ferrochelatase.
D000818:Animals; D002413:Cations, Divalent; D003035:Cobalt / Q000494:pharmacology; D003300:Copper / Q000378:metabolism* / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D006418:Heme / Q000096:biosynthesis*; D007501:Iron / Q000378:metabolism; D007504:Iron Radioisotopes; D007700:Kinetics; D007854:Lead / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008190:Lyases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008345:Manganese / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D011166:Porphyrins; D051381:Rats
D002413:Cations, Divalent; D007504:Iron Radioisotopes; D011166:Porphyrins; D007854:Lead; D003035:Cobalt; D006418:Heme; D008345:Manganese; D003300:Copper; D003577:Cytochrome P-450 Enzyme System; D007501:Iron; D008190:Lyases