Effect of citreoviridin and isocitreoviridin on beef heart mitochondrial ATPase.
Citreoviridin is a toxic metabolite from fungus that has been shown to be an inhibitor of mitochondrial F1-ATPases. Studies of citreoviridin, however, have been compromised by the light-dependent isomerization that it undergoes. The isomerization is a potential source of extensive variability in the studies, if citreoviridin and isocitreoviridin have different kinetic effects and binding properties. Both citreoviridin and isocitreoviridin recently have been purified and have been shown to be stable in the dark. Using the purified isomers, the effects of both citreoviridin and isocitreoviridin on soluble and membrane-bound beef heart mitochondrial F1-ATPase activity were investigated. It was found that citreoviridin was an uncompetitive inhibitor of ATP hydrolysis, and a non-competitive inhibitor of ITP hydrolysis catalyzed by soluble F1-ATPase. Isocitreoviridin had no effect on the hydrolysis of either of the triphosphates catalyzed by soluble F1-ATPase. The inhibition constant, Ki for citreoviridin was determined as 4.5 microM for ATP hydrolysis. The inhibition constants Kii and Kis for ITP hydrolysis were determined as 4.3 and 1.03 microM, respectively. Citreoviridin was an uncompetitive inhibitor of ATP hydrolysis and a noncompetitive inhibitor of ATP synthesis catalyzed by membrane-bound F1-ATPase. The inhibition constant, Ki, for ATP hydrolysis was around 4 microM. For ATP synthesis the inhibition constants were determined as 0.12 and 0.16 microM for Kis and Kii, respectively, when ADP concentration was kept saturating. Isocitreoviridin had no effect on either activity of the membrane-bound enzyme.
Sayood
S F
SF
Department of Chemistry, University of Nebraska, Lincoln 68588-0304.
Suh
H
H
Wilcox
C S
CS
Schuster
S M
SM
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001313:Aurovertins / Q000031:analogs & derivatives / Q000494:pharmacology*; D002417:Cattle; D002462:Cell Membrane / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D007293:Inosine Triphosphate / Q000378:metabolism; D007536:Isomerism; D007700:Kinetics; D008433:Mathematics; D008929:Mitochondria, Heart / Q000201:enzymology*; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors*; D011714:Pyrans / Q000494:pharmacology*
D001313:Aurovertins; D011714:Pyrans; D007293:Inosine Triphosphate; D000255:Adenosine Triphosphate; D006180:Proton-Translocating ATPases; C014416:citreoviridin