Mitochondrial NADH dehydrogenase

from Wikipedia, the free encyclopedia
Mitochondrial NADH dehydrogenase
Mitochondrial NADH dehydrogenase
Schematic representation of complex I in the inner mitochondrial membrane
Mass / length primary structure approx. 1000 kDa
Identifier
Gene name (s) NDH
Transporter classification
TCDB 3.D.1
designation Proton-translocating NADH dehydrogenase
Enzyme classification
EC, category 1.6.5.3 ,  oxidoreductase
Response type Redox reaction
Substrate NADH + ubiquinone
Products NAD + + ubiquinol

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

NADH + ubiquinone + 5 H + inside → NAD + + ubiquinol + 4 H + outside

mechanism

The redox reactions all take place in the hydrophilic, peripheral arm of the complex, which protrudes into the mitochondrial matrix. NADH binds to the tip of this arm in the nucleotide binding site and donates two electrons to the cofactor FMN and is thereby oxidized to NAD +. The electrons then pass through the electron transport chain, the centers of which, however, only accept one electron, so that the electrons are now divided: one is transferred to the iron-sulfur center N1a, the other to the iron-sulfur center N3 and from there continue via N1b, N4, N5, N6a, and N6b to the iron-sulfur center N2. From this last center of the electron transport chain, the electron is transferred to the second substrate ubiquinone, which is reduced to ubiquinol together with the second electron, which then also follows the same path. The only functional binding site for ubiquinone is at the contact point of the hydrophilic and hydrophobic part.

The (hydrophobic) membrane arm of the complex consists, among other things, of three antiporter- like subunits, which are believed to be involved in the translocation of protons. The exact mechanism of the translocation has not yet been clarified. During the last two steps of the electron transport chain, when the electrons are transferred to N2 and to ubiquinone, most of the energy is released, so that from here the energy is transferred to the antiporter-like subunits in a still unknown way.

Inhibitors

Rotenone and Piericidin A are two inhibitors that are structurally similar to ubiquinone and block the ubiquinone binding site , thus interrupting the electron transfer. Other inhibitors are Amytal and Asimicin . One NADH analog inhibitor that blocks the nucleotide binding site is adenosine diphosphate ribose . New studies show that the oral antidiabetic metformin from the group of biguanides is a weak but selective inhibitor of complex 1 in human hepatocytes. This leads to an increase in the cellular AMP / ATP quotient, which activates the AMP-dependent kinase. This activation of the AMPK has a variety of effects on the carbohydrate and lipid metabolism.

NAD (P) H dehydrogenase , which is Rotenone-insensitive, has formed as an alternative enzyme in plants .

See also

Other enzyme complexes of the mitochondrial respiratory chain :

literature

Web links