Concerted Two-Electron Reduction of Ubiquinone in Respiratory Complex I.

Area of Science:

• Biochemistry
• Molecular Biology
• Bioenergetics

Background:

• Respiratory complex I is crucial for cellular energy production.
• It catalyzes the reduction of ubiquinone (Q) to ubiquinole.
• The precise mechanism of this two-electron transfer remains unclear.

Purpose of the Study:

• To investigate a hypothetical concerted mechanism for the two-electron/two-proton reduction of ubiquinone by respiratory complex I.
• To evaluate the feasibility of simultaneous electron and proton transfer.

Main Methods:

• Development of a computational method to assess the coupling matrix element for concerted two-electron tunneling.
• Analysis of electron and proton transfer pathways involving key amino acid residues (His38, Tyr87) and the N2 FeS cluster.

Main Results:

• Calculations support a concerted reaction pathway for ubiquinone reduction.
• The proposed mechanism involves coupled electron/proton transfer from the N2 FeS cluster and His38.
• A hydrogen atom transfer from Tyr87 generates a transient tyrosyl radical.

Conclusions:

• The concerted reaction mechanism for respiratory complex I is computationally feasible.
• A transient tyrosyl radical is likely formed during the enzyme's catalytic cycle.
• This finding offers new insights into the complex electron transfer processes in cellular respiration.