Pages

Friday, May 2, 2014

Cellular respiration - Complex II

Probably at this point some of you are thinking: "Where have I heard that name before?" Actually, succinate dehydrogenase is the name of one of the enzymes of the Krebs cycle (specifically, the 6th enzyme!). This is the enzyme that promotes oxidation of succinate to fumarate. It is important to remember that all enzymes of the Krebs cycle, with one exception, are located in the mitochondrial matrix. The exception is exactly the succinate dehydrogenase, and now it is easy to understand why it is associated with the inner membrane – it takes also part of the mitochondrial respiratory chain! This is the only enzyme of the Krebs cycle which produces FADH2. And it is no coincidence that this happens because indeed, the function of complex II is to receive two electrons from FADH2 (from Krebs cycle) and to transport them to ubiquinone.
Complex II of the respiratory chain is called succinate dehydrogenase, and can also be called succinate:ubiquinone oxidoreductase.
I would like to take this opportunity to clarify something that is not always clear when one studies cellular respiration. It is often said that the complex II accepts electrons from FADH2 and transports them to ubiquinone. However, this information is not correct, because the FADH2 cofactor binds irreversibly to dehydrogenases. Therefore, in fact, only one FADH2 transfers the electrons to the complex II, the one formed in the same complex, that means, the FADH2 from the Krebs cycle. There are several metabolic pathways that also produce FADH2 (fatty acid oxidation, or the glycerol-3- phosphate shuttle, for example), but these FADH2 molecules transfer their electrons directly to ubiquinone, without passing through complex II.

Complex II represents an evolutionary adaptation of an enzyme thought to be initially solubilized in the mitochondrial matrix. However, during evolution it had to acquire the ability to bind to the membrane and interact with electronic carriers. It is the simplest complex of the respiratory chain in terms of number of subunits, and the sole complex of the respiratory chain that only performs electronic transfer without pumping protons into the intermembrane space. From the composition point of view we should highlight different redox cofactors , in particular Fe -S centers and a heme group (b heme). The redox centers and ubiquinone binding site are located on the membrane part, while the active center of succinate dehydrogenase is exposed to the mitochondrial matrix .


From a clinical standpoint, there are several diseases associated with mutations in genes encoding components of complex II, with emphasis on the relationship with diseases such as pheochromocytoma and paraganglioma.

No comments:

Post a Comment