Citrate Synthase: Difference between revisions
| Line 9: | Line 9: | ||
<scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/4' target='open' >active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, <scene name='Daniel_Eddelman_Sandbox_2/Asp_375/1' target='open' >Asp 375</scene> (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. <scene name='Daniel_Eddelman_Sandbox_2/His_274/1' target='open' >His 274</scene> stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and | <scene name='Daniel_Eddelman_Sandbox_2/Cts_active_site/4' target='open' >active site</scene> of citrate synthase participate in acid-base catalysis: His 274, His 320, and Asp 375. First, <scene name='Daniel_Eddelman_Sandbox_2/Asp_375/1' target='open' >Asp 375</scene> (a base) removes a proton from the methyl group of acetyl-CoA to form its enol. <scene name='Daniel_Eddelman_Sandbox_2/His_274/1' target='open' >His 274</scene> stabilizes the acetyl-CoA enolate by forming a hydrogen bond with the enolate oxygen. The enolate then nucleophilically attacks oxaloacetate’s carbonyl carbon, and | ||
<scene name='Daniel_Eddelman_Sandbox_2/His_320/1' target='open' >His 320</scene> donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA. | <scene name='Daniel_Eddelman_Sandbox_2/His_320/1' target='open' >His 320</scene> donates a proton to oxaloacetate’s carbonyl group in a concerted step, forming citryl-CoA (which remains bound to the enzyme). Finally, citryl-CoA is hydrolyzed to citrate and CoA. | ||
'''Regulation:''' Perhaps the most crucial regulators of the citrate synthase reaction are its substrates, acetyl-CoA and oxaloacetate. Both are present in the mitochondria at concentrations below saturation of citrate synthase. The metabolic flux is controlled by substrate availability, so controlling the levels of acetyl-CoA and oxaloacetate in the mitochondria controls the rate of reaction. Furthermore, citrate synthase is inhibited by NADH, citrate (which competes with oxaloacetate), and succinyl-CoA (an example of competitive feedback inhibition) <ref>PMID:3013232</ref>. | |||
<scene name='Daniel_Eddelman_Sandbox_2/Open_default/1' target='open' >Open Default</scene> | <scene name='Daniel_Eddelman_Sandbox_2/Open_default/1' target='open' >Open Default</scene> | ||