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Electron transport chain. NADH dehydrogenase is "I", at the left.

The structure of the peripheral domain of a NADH dehydrogenase related protein; bacterial FMN dehygrogenase PDB 2FUG. This structure omits a large transmembrane domain which lies to the bottom of the image and extends to the right. This section of the complex lies in the mitochondrial matrix.

The electron carriers of the NADH dehydrogenease complex. 7 primary iron sulphur centers lie in a line down the peripheral arm of the complex to carry electrons from the site of NADH dehydration to ubiquinone. The iron sulphur group on the right is not found in the eukaryotic complex. Note: This image includes two errors. At the top it should indicate NADH ---> NAD⁺ via a FMN electron carrier/cofactor. At the bottom it should indicate Ubiquinone ---> Ubiquinol.

NADH dehydrogenase (EC 1.6.5.3) 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.

It is the first enzyme (complex I) 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.

It 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 ^[1].

The structure is a L shape with a long membrane domain (with around 60 trans-membrane helices) and a hydrophilic peripheral domain which includes the NAD reducing activity. While 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) ^[2].

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

1. ^ Voet, D, & Voet, J. G, (2004) Biochemistry, 3rd Edition, John Wiley and Sons, pps 813-826
2. ^ Sazanov L.A., Hinchliffe P. (2006) Structure of the hydrophilic domain of respiratory complex I from Thermus thermophilus. Science 311, 1430-1436.

ETC

• Interactive Molecular model of NADH dehydrogenase (Requires MDL Chime)
• Complex I home page at The Scripps Research Institute
• MeSH Electron+Transport+Complex+I
• MeSH NADH+Dehydrogenase

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