The NADH Dehydrogenase Complex

The NADH dehydrogenase complex, also known as Complex I, is the first and largest enzyme complex in the electron transport chain (ETC) of cellular respiration. Its main function is to accept electrons from NADH and transfer them to coenzyme Q (CoQ), also known as ubiquinone, while pumping protons across the mitochondrial inner membrane (in eukaryotes) or the plasma membrane (in prokaryotes).

The functioning of the NADH dehydrogenase complex involves several steps:

1. Electron Transfer: The NADH dehydrogenase complex consists of numerous subunits that work together. The initial step is the transfer of two electrons from NADH to the flavin mononucleotide (FMN) cofactor, which is bound to the complex. This results in the reduction of FMN to FMNH2.
2. Iron-Sulfur Clusters: The reduced FMNH2 donates its electrons to a series of iron-sulfur (Fe-S) clusters within the complex. These clusters serve as electron carriers and are composed of iron atoms coordinated with sulfur atoms.
3. Coenzyme Q Binding Site: Once the electrons have been transferred through the Fe-S clusters, they are passed to coenzyme Q (CoQ), which is embedded in the lipid bilayer of the inner mitochondrial membrane. CoQ accepts the electrons and becomes reduced (CoQH2).
4. Proton Pumping: As electrons flow through the Fe-S clusters, the NADH dehydrogenase complex uses the energy released to pump protons (H+) across the membrane, from the matrix (or cytoplasm in prokaryotes) to the intermembrane space. This creates an electrochemical gradient, with a higher concentration of protons in the intermembrane space.

The proton pumping function of the NADH dehydrogenase complex contributes to the establishment of the proton gradient across the membrane, which is essential for ATP synthesis in the later steps of the electron transport chain. The energy stored in the electrochemical gradient drives the synthesis of ATP through the ATP synthase complex.

In addition to its electron transfer and proton pumping functions, the NADH dehydrogenase complex is involved in various other processes, including the regulation of reactive oxygen species (ROS) production, maintenance of cellular redox balance, and coordination of metabolic pathways.

Notably, the NADH dehydrogenase complex can be inhibited by certain compounds, such as rotenone. Inhibitors disrupt the flow of electrons through the complex, leading to a decrease in the production of ATP and impairing cellular respiration.