Ortho-quinone-enhanced ascorbate oxidation. Combined roles of lipid charge and the magnesium cation

Abstract

Quinones are widely distributed compounds in nature. Of these, ortho-quinones are found to be involved in the pathogenic mechanism of Parkinson's disease, in oxidative deaminations to free-radical redox reactions, and as intermediates in the pathways implicated in the carcinogenicity of 2,3- and 3,4-catechol estrogens. Addition of MgCl₂ to solutions of the hydrophobic ortho-quinones, 1,10-phenanthroquinone (PHQ) and beta-lapachone (LQ) enhances ascorbate oxidation in the absence or presence of large unilamellar vesicles (LUVs) of the neutral lipid dimyristoylphosphatidylcholine (DMPC), although initial rates of ascorbate oxidation are smaller in the presence of lipid as compared to its absence. Addition of this salt to solutions of the para-quinone 1,4-naphthoquinone (NQ) did not affect the ascorbate rate of oxidation in the absence or presence of DMPC. Addition of MgCl₂ to semiquinone solutions of PHQ or LQ in the presence or absence of DMPC increases semiquinone stability, as detected from the semiquinone disproportionation equilibrium displacement to semiquinone formation. Furthermore, MgCl₂ increases the partition of the ortho-semiquinones into the aqueous phase, although no such effect is observed for the semiquinone of NQ. For all the quinones under study, smaller rates of ascorbate oxidation and of semiquinone equilibrium concentration occur in the presence of negatively charged LUVs composed of an equimolar mixture of DMPC and dimyristoylphosphatidic acid DMPA. Ascorbate oxidation rate enhancements correlate with an increase in semiquinone concentration with addition of MgCl₂, in the absence or presence of neutral lipid. This observation favors the proposition that ascorbate oxidation rate increases are caused by semiquinone thermodynamic stabilization. Thus, the ascorbate oxidation rate enhancement by MgCl₂ in solutions containing hydrophobic ortho-quinones is still possible in systems with hydrophobic environments analogous to that of DMPC.

Keywords:

• Ortho-quinone
• semiquinone
• magnesium
• DMPC
• membrane
• ascorbate
• DMPA
• beta-lapachone
• phenanthroquinone
• naphthoquinone

Acknowledgements

The authors are grateful for grants No. SO6-GM008216, and P20 RR-016470 from NIH (USA) for financial support of this work.