Probing the ubiquinone reduction site in bovine mitochondrial complex I using a series of synthetic ubiquinones and inhibitors.
Studies of the structure-activity relationships of ubiquinones and specific inhibitors are helpful to probe the structural and functional features of the ubiquinone reduction site of bovine heart mitochondrial complex I. Bulky exogenous short-chain ubiquinones serve as sufficient electron acceptors from the physiological ubiquinone reduction site of bovine complex I. This feature is in marked contrast to other respiratory enzymes such as mitochondrial complexes II and III. For various complex I inhibitors, including the most potent inhibitors, acetogenins, the essential structural factors that markedly affect the inhibitory potency are not necessarily obvious. Thus, the loose recognition by the enzyme of substrate and inhibitor structures may reflect the large cavity like structure of the ubiquinone (or inhibitor) binding domain in the enzyme. On the other hand, several phenomena are difficult to explain by a simple one-catalytic site model for ubiquinone.
Miyoshi
H
H
Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Japan. miyoshi@kais.kyoto-u.ac.jp
D000818:Animals; D020134:Catalytic Domain; D002417:Cattle; D042967:Electron Transport Complex I; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D066298:In Vitro Techniques; D008929:Mitochondria, Heart / Q000201:enzymology; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D011726:Pyridinium Compounds / Q000737:chemistry / Q000494:pharmacology; D011806:Quinolinium Compounds / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism*
D004791:Enzyme Inhibitors; D011726:Pyridinium Compounds; D011806:Quinolinium Compounds; D014451:Ubiquinone; D009247:NADH, NADPH Oxidoreductases; D042967:Electron Transport Complex I