4) Pyruvate dehydrogenase (PDH) is a critical regulatory point of aerobic energy
ID: 219829 • Letter: 4
Question
4) Pyruvate dehydrogenase (PDH) is a critical regulatory point of aerobic energy metabolism. It is regulated though a process of phosphorylation/dephosphorylation shown in the diagram. Phosphorylation is the covalent addition of a Phosphate molecule to a substrate. The phosphate is added to PDH by the enzyme "PDH kinase". So, the action of PDH kinase inactivates PDH Dephosphorylation is the removal of the kinase from the substrate. The phosphate is removed from the inactive PDH by the enzyme "PDH phosphatase". So, the action of PDH phosphatase re-activates PDH. PDH inactive ADP H20 PDH PDH kinase tase ATP PDH active a) Let's consider an imaginary drug called "substance X". You observe that there is more AcetylCoA produced by PDH in the cell when substance X is added to cells Substance X does not affect the structure or activity of PDH Explain 2 ways by which substance X may affect acetylCoA production by PDH. (3 pts) pyruvate AcetylCo4 CoAst co NAD NADH b) Explain two ways phosphorylation can prevent the activity of PDH. (3 pts)Explanation / Answer
a. Pyruvate dehydrogenase catalyzes the oxidative decarboxylation of pyruvate to produce Acetyl CoA. PDH is activated by PDH-phosphatase while it is inactivated by PDH-kinase. The addition of phosphate group to PDH inactivates its function. It is given that Acetyl CoA levels are high in the cell when substance X was added. This can be due to
i. Substance X can be an activator of PDH phosphatase.
ii. Substance X can be an inhibitor of PDH kinase.
b. PDH is inactive when phosphorylated. The phosphorylation can inhibit enzyme action by
i. Changing the conformation of the active site so that substrate can no longer access it.
ii. It may change interacting partners of the protein or the enzyme may get sequestered/localized into a different cellular compartment.
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