Electron tunneling rates in respiratory complex I are tuned for efficient energy conversion

Angew Chem Int Ed Engl. 2015 Feb 23;54(9):2844-8. doi: 10.1002/anie.201410967. Epub 2015 Jan 19.

Abstract

Respiratory complex I converts the free energy of ubiquinone reduction by NADH into a proton motive force, a redox reaction catalyzed by flavin mononucleotide(FMN) and a chain of seven iron-sulfur centers. Electron transfer rates between the centers were determined by ultrafast freeze-quenching and analysis by EPR and UV/Vis spectroscopy. The complex rapidly oxidizes three NADH molecules. The electron-tunneling rate between the most distant centers in the middle of the chain depends on the redox state of center N2 at the end of the chain, and is sixfold slower when N2 is reduced. The conformational changes that accompany reduction of N2 decrease the electronic coupling of the longest electron-tunneling step. The chain of iron-sulfur centers is not just a simple electron-conducting wire; it regulates the electron-tunneling rate synchronizing it with conformation-mediated proton pumping, enabling efficient energy conversion. Synchronization of rates is a principle means of enhancing the specificity of enzymatic reactions.

Keywords: bioenergetics; electron tunneling; enzyme kinetics; metalloenzymes; reaction mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Electron Transport
  • Electron Transport Complex I / antagonists & inhibitors
  • Electron Transport Complex I / metabolism*
  • Energy Metabolism*
  • Escherichia coli / chemistry
  • Escherichia coli / metabolism
  • Flavin Mononucleotide / chemistry
  • Flavin Mononucleotide / metabolism
  • Iron-Sulfur Proteins / chemistry
  • Iron-Sulfur Proteins / metabolism
  • NAD / chemistry
  • NAD / metabolism
  • Oxidation-Reduction
  • Proton Pumps / metabolism
  • Pyridines / pharmacology

Substances

  • Iron-Sulfur Proteins
  • Proton Pumps
  • Pyridines
  • NAD
  • Flavin Mononucleotide
  • piericidin A
  • Electron Transport Complex I