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NADH dehydrogenase (EC 126.96.36.199) is an enzyme located in the inner mitochodrial membrane that catalyzes the transfer of electrons from NADH to coenzyme Q (CoQ). It is also called the NADH:quinone oxidoreductase.
NADH Dehydrogenase is the first enzyme (complex 1) of the mitochondrial electron transport chain.
- NADH + CoQ + 5H+ → NAD+ + CoQH2 + 4H+
In this process, the complex translocates protons across the inner membrane, helping to build the electrochemical potential used to produce ATP. The exact catalytic mechanism remains unknown.
Composition and structure
NADH Dehydrogenase is the largest of the respiratory complexes, the mammalian enzyme containing 42 separate polypeptide chains. Of particular functional importance are the flavin prosthetic group and eight iron-sulfur clusters. Of the 42 subunits, seven are encoded by the mitochondrial genome .
The structure is an "L" shape with a long membrane domain (with around 60 trans-membrane helices) and a hydrophilic peripheral domain, which includes the NAD-reducing activity. Whereas the structure of the eukaryotic complex is not well characterised, the peripheral/hydrophilic domain of the complex from a bacterium (Thermus thermophilus) has been crystallised (PDB: 2FUG) .
The best-known inhibitor of complex I is Rotenone (used as an organic pesticide). It is thought to bind to the ubiquinone binding site.
Piericidin A is a more potent inhibitor and is a close structural homologue of ubiquinone.
Mutations in the subunits of complex I can cause mitochondrial diseases, including Leigh syndrome.
There is some evidence that complex I defects may play a role in the etiology of Parkinson's disease, perhaps because of reactive oxygen species (complex I can, like complex II, leak electron to oxygen, forming highly toxic superoxide). In fact, recent investigations suggest that reverse electron transfer through Complex I might be the most important site of superoxide production within mitochondria.
- NDUFS1 - NADH dehydrogenase (ubiquinone) Fe-S protein 1, 75kDa (NADH-coenzyme Q reductase)
- NDUFS2 - NADH dehydrogenase (ubiquinone) Fe-S protein 2, 49kDa (NADH-coenzyme Q reductase)
- NDUFV1 - NADH dehydrogenase (ubiquinone) flavoprotein 1, 51kDa
- NDUFV2 - NADH dehydrogenase (ubiquinone) flavoprotein 2, 24kDa
- NDUFV3 - NADH dehydrogenase (ubiquinone) flavoprotein 3, 10kDa
- MT-ND4 - mitochondrially encoded NADH dehydrogenase 4
- ^ Voet, D, & Voet, J. G, (2004) Biochemistry, 3rd Edition, John Wiley and Sons, pps 813-826
- ^ Sazanov L.A., Hinchliffe P. (2006) Structure of the hydrophilic domain of respiratory complex I from Thermus thermophilus. Science 311, 1430-1436.