October 23, 2007
Electron Transport Shuttles in the Mitochondria
So in Mitochondria Pt. 2 I mention that thare are a few ways for NADH produced in the cytosol to enter the mitochondria to take part in ATP synthesis. I mentioned one of these ways: the Glycerol Phosphate Shuttle. Electrons from cytosolic NADH imported by the glycerol phosphate shuttle end up reducing FAD. However, the way in which they do this is of interest.
NADH from the cytosol gives up its two electrons and Hydrogen (becoming NAD+), to Dihydroxyacetone phosphate (DHAP). The keytone on DHAP is totally reduced, transforming DHAP into Glycerol 3-phosphate. Glycerol 3-phosphate will then float untill it encounters inner membrane bound Glycerol 3-phopshate dehydrogenase. G3PDH has a FAD prosthetic group attached to it, as shown in the figure to the left (the FAD group is the orange organic molecule inside the protein). When Glycerol 3-phosphate encounters G3PDH, it transfers its electrons to the FAD prosthetic group. This is now This has the effect of making FAD prosthetic group in a membrane bound protein oxidized. Ubiquinone can come along and encounter the FAD group, and take the electrons away, shuttling the electrons into the electron transport chain at the same point that electrons coming through Succinate dehydrogenase enter the chain. Thus cytosolic NADH electrons is equivalent to a mitochondria generated FAD electrons. In the process of giving up its electrons to G3PDH, Glycerol 3-phosphate re-oxidizes to form DHAP once more, and the cycle can begin again. This whole process is very nicely summed up in this schematic from Stryer’s Biochemistry Fifth Edition, which is available for free on the NCBI bookshelf.
However, the Glycerol Phosphate shuttle is not the only way that cytoslic reducing power can reach the electron transport chain. They can also enter through the Malate-Asparte shuttle, which is active in the heart and the liver. This process is also summed up by nice graphic from Stryler:
As shown, this cycle is significantly more complex, involving the reduction of Oxaloacetate into Malate, which then goes into the matrix through a Malate-α-Keytoglutarate antiporter (Malate in, α-Keytoglutarate out), where it is oxidized by NAD+ back into Oxaloacetate. This system transports in electrons at their full NADH energy state, allowing them to enter the electron transport chain via NADH dehydrogenase, and pump five protons across the membrane.
Unlike the Glycerol Phosphate Shuttle, this shuttle is fully reversible: excess NADH in the matrix transforms Oxalate into Malate, where it travels the reverse path (once its concentration is high enough) bringing α-keytoglutarate back in. Thus when the NADH concentration is high in the matrix, it is exported out, keeping the electron transport chain from becoming over reduced. (When this happens, superoxide [O2-] can be created, a very, very bad thing.) The transport of NADH out of the matrix slows glycolysis (substrate NAD+ is removed) and slows electron transport chain by lowering the concentration of NADH. In this way the NADH/NAD+ ratio is kept equal in both the mitochondria and the cytosol.
To sum it up:
Well thats all! The information for this post came from the What is Life site, Stryler’s Biochemistry Textbook and a discussion with Dr. David Borst, Professor of Biology at University of Central Florida.