Protein ubiquinone interaction. Synthesis and biological properties of 5-alkyl ubiquinone derivatives

J Biol Chem. 1994 Nov 11;269(45):27885-8.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkylation
  • Electron Transport Complex II
  • Electron Transport Complex III / metabolism*
  • Indicators and Reagents
  • Kinetics
  • Multienzyme Complexes / metabolism*
  • Oxidation-Reduction
  • Oxidoreductases / metabolism*
  • Structure-Activity Relationship
  • Succinate Cytochrome c Oxidoreductase / metabolism*
  • Succinate Dehydrogenase / metabolism*
  • Ubiquinone / analogs & derivatives*
  • Ubiquinone / chemical synthesis*
  • Ubiquinone / metabolism
  • Ubiquinone / pharmacology

Substances

  • Indicators and Reagents
  • Multienzyme Complexes
  • Ubiquinone
  • Oxidoreductases
  • Succinate Cytochrome c Oxidoreductase
  • Electron Transport Complex II
  • Succinate Dehydrogenase
  • Electron Transport Complex III