Pyrroloquinoline quinone acts with flavin reductase to reduce ferryl myoglobin in vitro and protects isolated heart from re-oxygenation injury.
Pyrroloquinoline quinone has been isolated from bacteria and recently has been detected in mammalian tissues and fluids. We report in vitro studies which show that pyrroloquinoline quinone serves as a high-affinity substrate for an erythrocyte "flavin reductase" and that the pyrroloquinoline quinol generated by this catalysis reacts rapidly with ferryl myoglobin radical. Western blot analysis of rat and rabbit heart homogenates detects a cross-reactive protein which has a molecular weight identical to the erythrocyte reductase from the same species. Low concentrations of pyrroloquinoline quinone protect isolated rabbit heart from re-oxygenation injury, serving as an effective tissue-protective agent in this model for cellular oxidative damage. We propose that this tissue protection is due to a pyrroloquinoline quinol-mediated reduction of reactive oxygen species.
Department of Biological Chemistry, Medical School, University of Michigan, Ann Arbor 48109.
F
F
Xu
C P
CP
Mack
K S
KS
Quandt
M
M
Shlafer
V
V
Massey
D E
DE
Hultquist
D000818:Animals; D003067:Coenzymes / Q000378:metabolism / Q000494:pharmacology*; D003429:Cross Reactions; D004912:Erythrocytes / Q000201:enzymology; D038181:FMN Reductase; D006736:Horses; D066298:In Vitro Techniques; D008786:Metmyoglobin / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction; D045542:PQQ Cofactor; D015363:Quinolones / Q000378:metabolism / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats
D003067:Coenzymes; D015363:Quinolones; C028048:ferrylmyoglobin; D008786:Metmyoglobin; D045542:PQQ Cofactor; D038181:FMN Reductase; D009247:NADH, NADPH Oxidoreductases