Lectures 22 & 23 The TCA Cycle-BW

Tca cycle oaa is ued by other pathways as well the

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Unformatted text preview: A is ued by other pathways as well. - the most rate limniting substrate in the mitondria - OAA binds fi rst and creates binding site of Actyl CoA aand carry out the reacitn. 4/6 and 4/8/13 MCB 2000 Lectures 22 & 23 Citrate Is Isomerized by Aconitase to Form Isocitrate Remove water molecule - make double bond between two carbons. add water back and moved carboxyl group to carbon 2 when it was at c arbon 3. Citrate is a poor substrate for oxidation So aconitase isomerizes citrate to yield isocitrate which has a secondary -OH, which can be oxidized Reaction involves a dehydration followed by hydration to enable an oxidative decarboxylation to occur in the next step. Isomerization necessary to carry out oxidation dehydrogenation 4/6 and 4/8/13 MCB 2000 Lectures 22 & 23 Isocitrate Dehydrogenase Catalyzes the First Oxidative Decarboxylation in the Cycle Rate-Limiting Step Isocitrate dehydrogenase is a link to the electron transport pathway because it makes NADH Rate of formation of -ketoglutarate determines the rate of the cycle. Rate liminting the fi rst step where you prduce NADH - NADH will donate electros to trasnport chain - linking the TCA c ycle to the elctron trasnport chain - going to work together. 4/6 and 4/8/13 MCB 2000 Lectures 22 & 23 Oxidation & Decarboxylation of Isocitrate First of four redox reactions: oxidation of alcohol group to keto group Classic NAD+ chemistry (hydride removal) followed by a Look at the reaction - the hydrozyl group - oxidize through carbil. lose CO2 - oxidiactive decarboxylation 4/6 and 4/8/13 MCB 2000 Lectures 22 & 23 Isocitrate Dehydrogenase Allosteric regulation: ADP & NADH Low energy charge. increase rate of some cycle. decline in activity of isocritrate dehydrogena se - feedback inhibited by NADH. Now add a 4th enzyme that is r egulated by energy charge. PFK pruvate kinase Pryuvate dehydrozase and cirtrate dehydrogenze - all regulated by energy charge. ADP increases s hift to left. differnet x-axis. more and more into low energy charge state. This allows the TCA cycle to respond to the energy level of the cell: High ADP means low ATP & High NADH means the ETC is functioning at capacity 4/6 and 4/8/13 MCB 2000 Lectures 22 & 23 -Ketoglutarate Dehydrogenase Thioester bond A second oxidative decarboxylation This enzyme is nearly identical to pyruvate dehydrogenase - structurally and mechanistically. Five coenzymes used - TPP, CoASH, Lipoic acid, NAD+, Use eneryg in thioester bond to carry out high enery phsophate. FAD 4/6 and 4/8/13 MCB 2000 Lectures 22 & 23 How Is Oxaloacetate Regenerated to Complete the TCA Cycle? (or ADP)** (or ATP)** Re **Tissue specificity Succinyl-CoA Synthetase A substrate-level phosphorylation A nucleoside triphosphate is made Its synthesis is driven by hydrolysis of a CoA thioester bond which is used to form GTP or ATP 4/6 and 4/8/13 MCB 2000 Lectures 22 & 23 Succinate Dehydrogenase Is FAD-Dependent Remove hdyrogen. FAD will accept. and now form...
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This note was uploaded on 09/17/2013 for the course MCB 2610 / 200 taught by Professor Feldman during the Fall '12 term at UConn.

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