chapter 18 discusses the complexities of the pyruvate dehydrogenase complex -- w
ID: 910191 • Letter: C
Question
chapter 18 discusses the complexities of the pyruvate dehydrogenase complex -- which has 3 main enzymes in it -- and some other control enzymes attached. Check out the reactions on pp 320 - 321. Add these three reactions, just using names, of course, and see if you can get the overall reaction for production of acetylCoA from pyruvate (and HSCoA, of course). Although there are three enzymes involved, it's really 5 reactions that should be summed to get the overall reaction -- make sure you work on both pages: 320 and 321.
Can someone please help me with the Overall reaction for production of acetylCoA from pyruvate (and HSCoA)? Thank you so much!
Explanation / Answer
Piruvate dehydrogenase catalyzed oxidative decarboxylation of Piruvate to form acetylCoA. This enzyme is a large complex containing many copies of three enzymes. E1 is Piruvate dehydrogenase. E2 is dihydrolipoyl transacetylase. E3 is dihydropoyl dehydrogenase. First the keto C of Piruvate reacts with the carbanion of TPP on E1 to yield an addition compound. The electron pulling charged N of the thiazole ring promotes CO2 loss. Hydroxyethyl-TPP remains. Then the hydroxyethyl carbanion on TPP of E1 reacts with the disulfide of lipoamine of E2. What was the keto C of Piruvate is oxidized to a carboxylic acid as the lipoamine disulfide is reduced to a dithiol. The acetate formed by oxidation of the hydroxyethyl is linked to one of the things of the reduced lipoamine as a thioester
then acetate is transferred from the thiol of lipoamine to the thiol of the coenzymeA yielding to acetylCoA . The reduced lipoamine swings over the E3 active site. Dihydrolipoamine is reoxidized to the disulfide as 2e- + 2H+ are transferred to a disulfide on E3. The dithiol on E3 is reoxidized as 2e-+2H+ transferred to FAD. The resulting FADH2 is reoxidized by electron transfer to NAD to yield NADH+H
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