Heme catabolism by the reconstituted heme oxygenase system.
The heme oxygenase system was reconstituted from heme oxygenase purified from pig spleen microsomes and NADPH-cytochrome c reductase purified from pig liver microsomes. The pig spleen heme oxygenase does not appear to involve cytochrome P-450 but seems to be a protein which readily binds heme to form a heme-protein complex which behaves as an active enzyme and consequently the heme on the enzyme protein is decomposed by its own oxidative activity. The sequence of heme decomposition by the reconstituted heme oxygenase system is quite similar to that in the non-enzymic coupled oxidation of myoglobin and ascorbic acid. In the reconstituted complete reaction system the stoichiometric ratio of decrease of heme, yield of biliverdin, oxidation of NADPH, and consumption of O2 was approximately 1:1:7--8:5--6 when the blank values were subtracted. In the reaction with the pig spleen microsomal preparation the stoichiometric ratio of the decrease of heme, yield of bilirubin, oxidation of NADPH, and consumption of O2 was approximately 1:0.8:9--10:6--7. Larger consumptions of NADPH AND O2 than expected may be due to side reactions. Hemopexin-heme complex was a poor substrate for heme oxygenase. Superoxide dismutase exerted no effect on either the rate or the stoichiometry of the heme oxygenase reaction. Catalase did not affect the rates of heme decomposition and NADPH oxidation, but reduced the rate of O2 consumption by about 30%.
D000818:Animals; D002374:Catalase / Q000494:pharmacology; D006418:Heme / Q000378:metabolism*; D006466:Hemopexin / Q000378:metabolism; D006801:Humans; D008861:Microsomes / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology; D009247:NADH, NADPH Oxidoreductases; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010101:Oxygen Consumption; D010105:Oxygenases; D013237:Stereoisomerism; D013482:Superoxide Dismutase / Q000494:pharmacology
D006418:Heme; D006466:Hemopexin; D002374:Catalase; D010105:Oxygenases; D013482:Superoxide Dismutase; D009247:NADH, NADPH Oxidoreductases; D009251:NADPH-Ferrihemoprotein Reductase