Medical College of Wisconsin
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Kinetics and regulation of mammalian NADH-ubiquinone oxidoreductase (Complex I). Biophys J 2010 Sep 08;99(5):1426-36

Date

09/08/2010

Pubmed ID

20816054

Pubmed Central ID

PMC2931722

DOI

10.1016/j.bpj.2010.06.063

Scopus ID

2-s2.0-77956604712 (requires institutional sign-in at Scopus site)   15 Citations

Abstract

NADH-ubiquinone oxidoreductase (Complex I, European Commission No. 1.6.5.3) is one of the respiratory complexes that generate the proton-motive force required for the synthesis of ATP in mitochondria. The catalytic mechanism of Complex I has not been well understood, due to the complicated structure of this enzyme. Here, we develop a kinetic model for Complex I that accounts for electron transfer from NADH to ubiquinone through protein-bound prosthetic groups, which is coupled to the translocation of protons across the inner mitochondrial membrane. The model is derived based on the tri-bi enzyme mechanism combined with a simple model of the conformational changes associated with proton transport. To study the catalytic mechanism, parameter values are estimated by analyzing kinetic data. The model is further validated by independent data sets from additional experiments, effectively explaining the effect of pH on enzyme activity. Results imply that matrix pH significantly affects the enzyme turnover processes. The overall kinetic analysis demonstrates a hybrid ping-pong rapid-equilibrium random bi-bi mechanism, consolidating the characteristics from previously reported kinetic mechanisms and data.

Author List

Chen X, Qi F, Dash RK, Beard DA

Author

Ranjan K. Dash PhD Professor in the Biomedical Engineering department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Biocatalysis
Biological Transport
Cattle
Electron Transport Complex I
Hydrogen-Ion Concentration
Kinetics
Mammals
Mitochondria
Mitochondrial Membranes
Models, Biological
Myocardium
Protons
Rats
Reproducibility of Results