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The activity of the pyruvate dehydrogenase complex is also controlled by phosphorylation. Pyruvate dehydrogenase kinase (PDH kinase) catalyzes the phosphorylation of a specific Ser residue on the E1 subunit of the enzyme, rendering it inactive. Pyruvate dehydrogenase phosphatase (PDH phosphatase) reverses the inhibition by catalyzing the removal of this phosphate group. The PDH kinase is highly regulated and its activity is influenced by various cellular metabolites. Indicate whether the following would activate or inhibit PDH kinase:
Inhibit or activate PDK?
NAD+ activate
NADH inhibit
coenzyme A activate
acetyl-CoA inhibit
ADP inhibit
Did I answer these correctly?

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Answer:

Increase in [NAD+] inhibits Pyruvate dehydrogenase kinase (PDH kinase)

Increase in [NADH] activates Pyruvate dehydrogenase kinase (PDH kinase)

Coenzyme A inhibits Pyruvate dehydrogenase kinase (PDH kinase)

Acetyl-co A activates Pyruvate dehydrogenase kinase (PDH kinase)

ADP inhibits Pyruvate dehydrogenase kinase (PDH kinase)

Explanation:

Pyruvate dehydrogenase kinase, PDK is an enzyme which acts to inhibit the activity of the enzyme pyruvate dehydrogenase by phosphorylating it using ATP. It mechanism of action is by catalyzing the phosphorylation of a specific Ser residue on the E1 subunit of the pyruvate dehydrogenase complex, rendering it inactive. By inhibiting the activity of the pyruvate dehydrogenase complex, PDK will decrease the oxidation of pyruvate to acpcetyl-coA and CO₂ in the mitochondria and increase the conversion of pyruvate to lactate in the cytosol.

Since pyruvate dehydrogenase complex is activated by either an increase in the concentration of one or more of ADP, NAD+ or CoA-SH, its inhibitor pyruvate dehydrogenase kinase is inhibited by ADP, NAD+, CoA-SH and pyruvate. However, PDK is activated by increase in the concentration of ATP, NADH and acetyl-CoA.

Therefore, the correct answers are:

Increase in [NAD+] inhibits Pyruvate dehydrogenase kinase (PDH kinase)

Increase in [NADH] activates Pyruvate dehydrogenase kinase (PDH kinase)

Coenzyme A inhibits Pyruvate dehydrogenase kinase (PDH kinase)

Acetyl-co A activates Pyruvate dehydrogenase kinase (PDH kinase)

ADP inhibits Pyruvate dehydrogenase kinase (PDH kinase)

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