Editing Oxidative phosphorylation (section)

=== NADH-coenzyme Q oxidoreductase (complex I) ===
[[File:Complex I.svg|350px|thumb|right|Complex I or [[NADH dehydrogenase|NADH-Q oxidoreductase]]. The abbreviations are discussed in the text. In all diagrams of respiratory complexes in this article, the matrix is at the bottom, with the intermembrane space above.{{image reference needed|date=December 2022}}]]

[[NADH dehydrogenase|NADH-coenzyme Q oxidoreductase]], also known as ''NADH dehydrogenase'' or ''complex I'', is the first protein in the electron transport chain.<ref name=Hirst>{{cite journal | vauthors = Hirst J | title = Energy transduction by respiratory complex I--an evaluation of current knowledge | journal = Biochemical Society Transactions | volume = 33 | issue = Pt 3 | pages = 525–529 | date = June 2005 | pmid = 15916556 | doi = 10.1042/BST0330525 }}</ref> Complex I is a giant [[enzyme]] with the mammalian complex I having 46 subunits and a molecular mass of about 1,000 [[atomic mass unit|kilodaltons]] (kDa).<ref name=Lenaz2006>{{cite journal | vauthors = Lenaz G, Fato R, Genova ML, Bergamini C, Bianchi C, Biondi A | title = Mitochondrial Complex I: structural and functional aspects | journal = Biochimica et Biophysica Acta (BBA) - Bioenergetics | volume = 1757 | issue = 9–10 | pages = 1406–1420 | year = 2006 | pmid = 16828051 | doi = 10.1016/j.bbabio.2006.05.007 | doi-access = free }}</ref> The structure is known in detail only from a bacterium;<ref name="thermophilus1">{{cite journal | vauthors = Sazanov LA, Hinchliffe P | title = Structure of the hydrophilic domain of respiratory complex I from Thermus thermophilus | journal = Science | volume = 311 | issue = 5766 | pages = 1430–1436 | date = March 2006 | pmid = 16469879 | doi = 10.1126/science.1123809 | s2cid = 1892332 | doi-access = free | bibcode = 2006Sci...311.1430S }}</ref><ref name="Ecoli">{{cite journal | vauthors = Efremov RG, Baradaran R, Sazanov LA | title = The architecture of respiratory complex I | journal = Nature | volume = 465 | issue = 7297 | pages = 441–445 | date = May 2010 | pmid = 20505720 | doi = 10.1038/nature09066 | s2cid = 4372778 | bibcode = 2010Natur.465..441E }}</ref> in most organisms the complex resembles a boot with a large "ball" poking out from the membrane into the mitochondrion.<ref>{{cite journal | vauthors = Baranova EA, Holt PJ, Sazanov LA | title = Projection structure of the membrane domain of Escherichia coli respiratory complex I at 8 A resolution | journal = Journal of Molecular Biology | volume = 366 | issue = 1 | pages = 140–154 | date = February 2007 | pmid = 17157874 | doi = 10.1016/j.jmb.2006.11.026 }}</ref><ref>{{cite journal | vauthors = Friedrich T, Böttcher B | title = The gross structure of the respiratory complex I: a Lego System | journal = Biochimica et Biophysica Acta (BBA) - Bioenergetics | volume = 1608 | issue = 1 | pages = 1–9 | date = January 2004 | pmid = 14741580 | doi = 10.1016/j.bbabio.2003.10.002 | doi-access = free }}</ref> The genes that encode the individual proteins are contained in both the [[cell nucleus]] and the [[mitochondrial genome]], as is the case for many enzymes present in the mitochondrion.

The reaction that is catalyzed by this enzyme is the two electron oxidation of [[Nicotinamide adenine dinucleotide|NADH]] by [[coenzyme Q10]] or ''ubiquinone'' (represented as Q in the equation below), a lipid-soluble [[quinone]] that is found in the mitochondrion membrane:

{{NumBlk|:|<chem>NADH + Q + 5H+_{matrix} -> NAD+ + QH2 + 4H+_{intermembrane}</chem>|{{EquationRef|1}}}}

The start of the reaction, and indeed of the entire electron chain, is the binding of a NADH molecule to complex I and the donation of two electrons. The electrons enter complex I via a [[prosthetic group]] attached to the complex, [[flavin mononucleotide]] (FMN). The addition of electrons to FMN converts it to its reduced form, FMNH<sub>2</sub>. The electrons are then transferred through a series of iron–sulfur clusters: the second kind of prosthetic group present in the complex.<ref name="thermophilus1"/> There are both [2Fe–2S] and [4Fe–4S] iron–sulfur clusters in complex I.

As the electrons pass through this complex, four protons are pumped from the matrix into the intermembrane space. Exactly how this occurs is unclear, but it seems to involve [[conformational change]]s in complex I that cause the protein to bind protons on the N-side of the membrane and release them on the P-side of the membrane.<ref>{{cite journal | vauthors = Hirst J | title = Towards the molecular mechanism of respiratory complex I | journal = The Biochemical Journal | volume = 425 | issue = 2 | pages = 327–339 | date = December 2009 | pmid = 20025615 | doi = 10.1042/BJ20091382 }}</ref> Finally, the electrons are transferred from the chain of iron–sulfur clusters to a ubiquinone molecule in the membrane.<ref name=Hirst/> Reduction of ubiquinone also contributes to the generation of a proton gradient, as two protons are taken up from the matrix as it is reduced to [[ubiquinol]] (QH<sub>2</sub>).