Protein ubiquinone interaction. Synthesis and biological properties of 5-alkyl ubiquinone derivatives.
For the investigation of the protein-ubiquinone interaction in the succinate-cytochrome c reductase region of the bovine heart mitochondrial electron transport chain, a series of 5-alkyl-substituted ubiquinone derivatives (5-R-Q0C10) were synthesized and characterized. Syntheses of 5-ethyl-Q0C10, 5-propyl-Q0C10, 5-isopropyl-Q0C10, and 5-butyl-Q0C10, were archived through radical coupling reactions between 2,3-dimethoxy-6-decyl-1,4-benzoquinone (5-H-Q0C10) and the corresponding alkanoyl peroxides. Although the spectral and redox properties of 5-R-Q0C10 are very similar to those of 5-methyl-2,3 dimethoxy-6-decyl-1,4-benzoquinone, the biological electron transfer efficiencies of these derivatives differ significantly. The reducibility of these derivatives by succinate, as measured with succinate-Q reductase and the oxidizability as measured by ubiquinol-cytochrome c reductase, decreased as the size of the substituents increased. 5-Ethyl-Q0C10 has about 50% of the activity of 5-methyl-2,3-dimethoxy-6-decyl-1,4-benzoquinone, whereas molecules with 5-alkyl groups of three or more carbon atoms are virtually inactive as electron acceptors for succinate-Q reductase. Reduced form of the derivative with no substituent at the 5-position, 5-H derivative is more effectively oxidized by ubiquinol-cytochrome c reductase than does the 5-methyl derivative, the native form. The oxidation of 5-H derivative is in a concentration-dependent manner at low concentrations but exhibits a substrate inhibition at higher concentrations. No such substrate inhibition is observed when other 5-substituted Q derivatives are used. 5-H derivative is a better electron acceptor for succinate-Q reductase than any other Q derivatives and does not show substrate inhibition, even at high concentrations. These results indicate that the binding environment of the benzoquinone ring in succinate-Q reductase is more specific than that of ubiquinol-cytochrome c reductase.
Department of Biochemistry, Oklahoma State University, Stillwater 74078.
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D000478:Alkylation; D042963:Electron Transport Complex II; D014450:Electron Transport Complex III / Q000378:metabolism*; D007202:Indicators and Reagents; D007700:Kinetics; D009097:Multienzyme Complexes / Q000378:metabolism*; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013384:Succinate Cytochrome c Oxidoreductase / Q000378:metabolism*; D013385:Succinate Dehydrogenase / Q000378:metabolism*; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology
D007202:Indicators and Reagents; D009097:Multienzyme Complexes; D014451:Ubiquinone; D010088:Oxidoreductases; D013384:Succinate Cytochrome c Oxidoreductase; D042963:Electron Transport Complex II; D013385:Succinate Dehydrogenase; D014450:Electron Transport Complex III