Glyceraldehyde-3-Phosphate Dehydrogenase: Difference between revisions

The mechanism of the glycolysis reaction is fairly straight forward.  After the aldehyde enters the <scene name='Nathan_Line_sandbox_3/Active_site/3'>active site</scene> (highlighted in green), the sulfhydryl group from <scene name='Nathan_Line_sandbox_3/Cystine/7'>Cystine 151</scene> attacks the nucleophilic carbon to form a thiohemiacetal.  This intermediate undergoes oxidation due to a hydride transfer to a nearby NAD+ forming a thioester.  From here, a phosphate group enters and attacks the same carbonyl while at the same time it is separated from the cystine by the protonated <scene name='Nathan_Line_sandbox_3/Histidine/5'>Histidine 178</scene> group.  This produces the desired 1,3-bisphosphoglycerate.  Though cystine-151 and histidine-178 are direct contributers to the catalytic process, other residues also influence the activity of this enzyme indirectly.  <scene name='Nathan_Line_sandbox_3/Other/2'>Thr-210 and Arg-233</scene> are two such residues that contribute to the binding of the reactants rather than the catalytic mechanism.  Regulation of GAPDH occurs through its coupling with the PGK reaction.  This coupling is needed due to the slightly positive delta G of the glycolysis.  The larger negative delta G of the PGK reaction results in the following overall net reaction with a delta G of -12.1 kJ/mol: