NADH dehydrogenase (ubiquinone)

The enzyme NADH dehydrogenase, NADH accurate: called coenzyme Q oxidoreductase ( systematic name ), also complex I of the mitochondrial respiratory chain, is an oxidoreductase. The enzyme catalyzes in a coupled reaction, the oxidation of NADH to the reduction of coenzyme Q and combines this with the translocation of protons from the matrix space ( indoor) in the intermembrane space ( outside) of the mitochondrion:


The redox reactions all take place in the hydrophilic peripheral arm of the complex, which projects into the mitochondrial matrix. NADH binds to the tip of this arm in the nucleotide binding site and two electrons to the FMN cofactor and then it becomes oxidized to NAD . The electrons then pass through the electron transport chain, but take their centers just one electron, so that the electrons are now split: one is transferred to the iron-sulfur center N1a, the other from the iron-sulfur center N3 and from there further on N1b, N4, N5, N6A and N6b the iron-sulfur center N2. Of this final center of the electron transport chain to the second substrate, the electron ubiquinone is transmitted which is reduced together with the second electron, which is then also the same way to ubiquinol. The only functional binding site for ubiquinone is located at the junction of the hydrophilic and hydrophobic part.

The (hydrophobic ) Membranarm of the complex consists among other things of three antiporter -like subunits, one of which is thought to be involved in the translocation of protons. The exact mechanism of translocation is not yet clear. In the last two steps of the electron transport chain in the transfer of electrons to N2 and ubiquinone, most of the energy is released, so that from here on as yet unknown type, the energy is transferred to the antiporter -like subunits.


Rotenone and piericidin A two inhibitors that have structural similarity to ubiquinone and block the Ubichinonbindestelle, the electron transfer is thus interrupted. Other inhibitors amytal and Asimicin. An NADH analog Inihibtor blocking the nucleotide binding site is Adenosindiphosphatribose. New studies show that the oral antidiabetic agent metformin from the biguanide is a weak but selective inhibitor of complex 1 in human hepatocytes. This leads to an increase in the cellular AMP / ATP ratio, resulting in an activation of AMP - dependent kinase result. This activation of AMPK has multiple effects on carbohydrate and lipid metabolism.