As we discussed in class, arsenite (HAsO3) and organic arsenicals (R-As=O), are irreversible inhibitors ofthe pyruvate dehydrogenase complex. Are there other compounds that might inhibit the complex in thesame way?
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The PDC is a crucial enzyme complex that converts pyruvate into acetyl-CoA, linking glycolysis to the citric acid cycle. It requires several cofactors, including thiamine (vitamin B1), and is sensitive to various inhibitors. Show more…
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Trivalent arsenic-containing compounds such as arsenite, AsO3-, can react readily with dithiols such as lipoamide to form arsenic adducts that are irreversible inhibitors of enzymes that require a dithiol (such as lipoamide of E2 of pyruvate dehydrogenase complex) for catalysis. Refer to reaction below: Arsenite + Dihydrolipoamide -> Arsenic-enzyme complex + 2 H2O Arsenite is therefore highly poisonous and would most likely inhibit which process?
Adi S.
Arsenate Poisoning Arsenate is structurally and chemically similar to inorganic phosphate $\left(\mathrm{P}_{\mathrm{i}}\right),$ and many enzymes that require phosphate will also use arsenate. Organic compounds of arsenate are less stable than analogous phosphate compounds, however. For example, acyl arsenates decompose rapidly by hydrolysis: (EQUATION CANNOT COPY) On the other hand, acyl phosphates, such as 1,3 -bisphosphoglycerate, are more stable and undergo further enzyme-catalyzed transformation in cells. (a) Predict the effect on the net reaction catalyzed by glyceraldchyde 3 -phosphate dehydrogenase if phosphate were replaced by arsenate. (b) What would be the consequence to an organism if arsenate were substituted for phosphate? Arsenate is very toxic to most organisms. Explain why.
Arsenate is structurally and chemically similar to inorganic phosphate $\left(P_{i}\right),$ and many enzymes that require phosphate will also use arsenate. Organic compounds of arsenate are less stable than analogous phosphate compounds, however. For example, acyl arsenates decompose rapidly by hydrolysis: On the other hand, acyl phosphates, such as 1,3 -bisphosphoglycerate, are more stable and undergo further enzyme-catalyzed transformation in cells. (a) Predict the effect on the net reaction catalyzed by glyceraldehyde 3 -phosphate dehydrogenase if phosphate were replaced by arsenate. (b) What would be the consequence to an organism if arsenate were substituted for phosphate? Arsenate is very toxic to most organisms. Explain why.
Josee P.
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