Isocitrate dehydrogenase: Difference between revisions
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<scene name='Michael_nobbe_sandbox_2/Isocitrate_active_site/2'>Active Site</scene> | <scene name='Michael_nobbe_sandbox_2/Isocitrate_active_site/2'>Active Site</scene> | ||
=='''Function'''== | |||
Isocitrate dehydrogenase is a digestive enzyme that is used in the citric acid cycle. Its main function is to catalyze the oxidative decarboxylation of isocitrate into alpha-ketoglutarate. Human isocitrate dehydrogenase is regulation is not fully understood however, it is known that NADP and Ca2+ bind in the active site to create three different conformations. These conformations form in the active site and are as follows: a loop is form in the inactive enzyme, a partially unraveled alpha helix in the semi open form, and a alpha helix in the active form<ref>PMID:15173171</ref>. Bacterial isocitrate dehydrogenase uses phosphorylation for regulation. The Ser94 residue undergoes reversible phosphorylation causing structural changes in the active site which hinders the catalytic function of the enzyme <ref>PMID:15173171</ref>. | |||
=='''Mechanism'''== | |||
The mechanism described is for porcine isocitrate dehydrogenase because is is better understood than the human mechanism. The alcohol group off the alpha-carbon is deprotonated by the Tyr residue. The electrons pust to the oxygen atom to form a double bond (keytone). The remaining alpha carbon hydrogen is removed using NAD+/NADP+ as an electron accepting cofactor. A carboxyl group pushes electrons down so an oxygen steals a nearby proton off a Lysine amino acid. The Tyr deprotanates the carboxylic acid resulting in electron pushing that ejects a CO2. The two negatively charged oxygens on the other side of the molecule are stabilized by the Mn2+. The double bond that was formed between the alpha and beta carbon removes a proton from the Tyr residue and the oxygen returns the a keytone and the alpha-ketoglutarate is formed. This is illustrated in the figure below. | |||
=='''References'''== | =='''References'''== | ||