Loss and degradation of enzyme-bound heme induced by cellular nitric oxide synthesis.
We report here that, like nonheme iron, protein-bound intracellular heme iron is also a target for destruction by endogenously produced nitric oxide (NO). In isolated rat hepatocytes NO synthesis results in substantial (approximately 60%) and comparable loss of catalase and cytochrome P450 as well as total microsomal heme, and decreased heme synthetic (delta-aminolevulinate synthetase and ferrochelatase) and increased degradative (heme oxygenase) enzymatic activities. The effect is reversible, and intact cytochrome P450 apoproteins are still present, as judged by heme reconstitution of isolated microsomes. The effects on delta-aminolevulinate synthetase and heme oxygenase are likely to be secondary to heme liberation, while the effects on ferrochelatase appear to be a direct effect of NO, perhaps destruction of its nonheme iron-sulfur center.
Kim
Y M
YM
Department of Surgery, University of Pittsburgh School of Medicine, Pennsylvania 15261.
Bergonia
H A
HA
Müller
C
C
Pitt
B R
BR
Watkins
W D
WD
Lancaster
J R
JR
D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism*; D002478:Cells, Cultured; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D016207:Cytokines / Q000494:pharmacology*; D006418:Heme / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000494:pharmacology / Q000502:physiology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D026423:S-Nitroso-N-Acetylpenicillamine; D014665:Vasodilator Agents / Q000494:pharmacology*; D019323:omega-N-Methylarginine
D016207:Cytokines; D012333:RNA, Messenger; D014665:Vasodilator Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D006418:Heme; D026423:S-Nitroso-N-Acetylpenicillamine; D003577:Cytochrome P-450 Enzyme System; D001120:Arginine; D007501:Iron; D002374:Catalase; D010396:Penicillamine