Enzymatic oxidation of cobalt protoporphyrin IX: observations on the mechanism of heme oxygenase action.
Studies on the enzymatic mechanism of microsomal heme oxygenase were made utilizing various porphyrins and metalloporphyrins of different ring substituents and central metal ions. Co-heme (cobalt protoporphyrin IX) was shown to be a substrate for the enzyme and the product of its oxidative metabolism was identified as the natural bile pigment, biliverdin IXalpha isomer. Metalloporphyrins, which do not bind molecular oxygen (Ni, Mn, and Sn protoporphyrin IX), were not substrates for heme oxygenase, although they could competitively inhibit oxidation of reactive substrates for the enzyme. The presence of lipophilic substitutents on pyrrole rings I and II, as well as a central metal atom, were required for the heme oxidation reaction to occur. The oxidative cleavage of Co-heme displayed typical characteristics of an enzyme-mediated reaction, and the oxidation of this substrate, as well as that of Fe-heme (iron protoporphyrin IX), could be supported with either reduced nicotinamide adenine dinucleotide phosphate or reduced nicotinamide adenine dinucleotide. A hypothesis is proposed on the mode of action of heme oxygenase in which the enzyme and its substrate are considered to form a "transitory" hemoprotein which can activate molecular oxygen for cleavage of the heme tetrapyrrole ring. In this formulation, heme as substrate for heme oxygenase is synonymous with heme as prosthetic group for the enzyme.
D000818:Animals; D001853:Bone Marrow / Q000201:enzymology; D003035:Cobalt; D006418:Heme / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008264:Macrophages / Q000201:enzymology; D008297:Male; D008861:Microsomes / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009532:Nickel / Q000494:pharmacology; D010084:Oxidation-Reduction; D011166:Porphyrins; D011524:Protoporphyrins; D051381:Rats
D011166:Porphyrins; D011524:Protoporphyrins; D003035:Cobalt; D006418:Heme; D009532:Nickel; D006899:Mixed Function Oxygenases