Citrate Synthase: Difference between revisions

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'''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington. In this mechanism, three ionizable side chains in the

<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' >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'>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'>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'>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, <scene name='Daniel_Eddelman_Sandbox_2/Citrate/2'>citrate</scene> (which competes with oxaloacetate), and succinyl-CoA (an example of competitive feedback inhibition) <ref>PMID:3013232</ref>.

Citrate Synthase: Difference between revisions

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@@ Line 8: / Line 8: @@
 '''Mechanism:''' The reaction mechanism for citrate synthase was proposed by James Remington.  In this mechanism, three ionizable side chains in the
-<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' >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'>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'>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'>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, <scene name='Daniel_Eddelman_Sandbox_2/Citrate/2'>citrate</scene> (which competes with oxaloacetate), and succinyl-CoA (an example of competitive feedback inhibition) <ref>PMID:3013232</ref>.