DBHBM (3,5-dibromo-4-hydroxy-benzylidenemalonitrile) is a novel inhibitor of electron transfer through the QN center of the mitochondrial bc1 complex.
DBHBM (3,5-dibromo-4-hydroxy-benzylidenemalonitrile) inhibited the NADH- or succinate-supported rate of O2 consumption in beef heart submitochondrial particles (Ki = 7 x 10(-7) M). Oxygen comsumption was restored with the addition of ascorbate/TMPD, indicating that the inhibitory effect was on the ubiquinol-cytochrome c reductase activity of the respiratory chain. Difference spectra with submitochondrial particles indicated that DBHBM blocked electron transport through the cytochrome bc1 complex, in a mode closely similar to that of antimycin A. The reduction rates of cytochrome b by succinate were strongly inhibited in the presence of DBHBM plus myxothiazol, but not by DBHBM plus antimycin A. These data suggest that DBHBM may bind primarily to the QN center. In the purified bc1 complex, DBHBM and antimycin A induced a red shift from 562 to 566 nm of the alpha peak of cytochrome b, supporting the idea that DBHBM influences predominantly the ligand field of the b562 (bh) heme. Difference spectra in the presence or absence of myxothiazol showed that DBHBM induced the same red shift with a maximum at 565 nm and a minimum at 559 nm. We conclude that DBHBM blocks electron transfer at the QN center and thus may be considered a novel group III inhibitor of the bc1 complex.
Lotina-Hennsen
B
B
Departamento de Bioquímica, Facultad de Química, Universidad Nacional Autónoma de México, México, D.F.
González-Halphen
D
D
Uribe
S
S
Rangel
P
P
Gómez-Lojero
C
C
D000818:Animals; D000968:Antimycin A / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D001665:Binding Sites; D002417:Cattle; D004579:Electron Transport / Q000187:drug effects; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors* / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008689:Methacrylates; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D009570:Nitriles / Q000378:metabolism / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D013053:Spectrophotometry; D013367:Submitochondrial Particles / Q000187:drug effects / Q000378:metabolism; D013386:Succinates / Q000378:metabolism; D019802:Succinic Acid; D013772:Tetramethylphenylenediamine / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D008689:Methacrylates; D009570:Nitriles; D013386:Succinates; D013844:Thiazoles; D009243:NAD; C093115:3,5-dibromo-4-hydroxybenzylidenemalonitrile; D000968:Antimycin A; C030517:myxothiazol; D019802:Succinic Acid; D014450:Electron Transport Complex III; D013772:Tetramethylphenylenediamine; D001205:Ascorbic Acid