Pyruvate Dehydrogenase

What is the primary function of the Pyruvate Dehydrogenase complex?

It catalyzes the oxidative decarboxylation of pyruvate to form Acetyl CoA, acting as the bridge between glycolysis and the Citric Acid Cycle.

Where is the PDH complex located within the cell?

The mitochondrial matrix.

What are the three enzyme components of the PDH complex?

1. E1: Pyruvate dehydrogenase component

2. E2: Dihydrolipoyl transacetylase

3. E3: Dihydrolipoyl dehydrogenase

Which prosthetic group/coenzyme is associated with the E1 component?

TPP (Thiamine pyrophosphate).

What is the role of the "Lipoamide swinging arm" in E2?

It carries the acetyl group between active sites, increasing efficiency by ensuring reactants do not leave the complex and stay in close proximity.

Is the conversion of pyruvate to Acetyl CoA reversible or irreversible in animal cells?

Irreversible. This is a key commitment step in metabolism.

How is the PDH complex regulated by covalent modification?

Inactivated by phosphorylation (via a kinase).

Activated by dephosphorylation (via a phosphatase).

Which hormone activates the PDH phosphatase to turn the enzyme on?

Insulin (signals that glucose is available to be used for energy or storage).

What are the primary allosteric inhibitors of the PDH complex?

High energy signals: ATP, Acetyl CoA, and NADH.

Why does glucagon stimulate the kinase that inactivates PDH?

When glucose is low, the body wants to save pyruvate for gluconeogenesis (making new glucose) rather than breaking it down for energy.

What are the five total coenzymes required by the PDH complex?

TPP

Lipoic acid (Lipoamide)

CoA

FAD

What are the three chemical steps to synthesize acetyl CoA from pyruvate

decarboxylation, oxidation, and transfer to coA

What is the prosthetic group and reaction catalyzed by E1

Tpp and oxidative decarboxylation of pyruvate

What is the prosthetic group and reaction catalyzed by E2

lipoamide

• transfer of acetyl group to CoA

What is the prosthetic group and reaction catalyzed by E3

FAD

• regeneration of the oxidized form of lipoamide

how it lipoamide coenzyme formed

by the attachment of the vitamin lipoic acid to a lysine residue in another enzyme in the complex, E2

What is the primary method of covalent modification used to regulate the Pyruvate Dehydrogenase (PDH) complex?

Phosphorylation and Dephosphorylation of the E1 enzyme subunit.

In what state is the $E_1$ enzyme active? In what state is it inactive?

* Active: Dephosphorylated (no phosphate group).Inactive: Phosphorylated (phosphate group attached to serine residues).

What is the role of the kinase associated with the E2 and E3 subunits?

It phosphorylates E1 at a serine residue, which inactivates the enzyme complex.

Why does glucagon activate the PDH kinase, and what is the metabolic goal?

Glucagon signals that glucose is low. Activating the kinase shuts down PDH to stop the conversion of pyruvate to Acetyl-CoA, thereby saving pyruvate for gluconeogenesis (making more glucose).

What is the role of the phosphatase associated with the PDH complex?

It removes the phosphate group from E1, which activates the enzyme.

What are two major activators of the PDH phosphatase mentioned in the notes?

* Insulin: Signals high blood sugar (time to process glucose).Ca^{2+} (Calcium): Specifically in muscles, signaling the need for energy production during contraction.

Look at the handwritten note: "E1 is active when dephosphorylated by kinase." Is this statement entirely correct?

No. While E1 is active when dephosphorylated, it is dephosphorylated by a phosphatase, not a kinase. Kinases add phosphates; phosphatases remove

What inhibits the pyruvate dehydrogenase

ATP, acetyl coA, and NADH

What stimulates the pyruvate dehydrogenase complex

ADP and pyruvate

What are the advantages of organizing the enzymes that catalyze the formation of acetyl coA from pyruvate into a single large complex

• rxn facilitated by close proximity

• lipoamide swinging arm speeds up process

• reactants don’t leave complex, more efficient

• enzymes in correct ratio

• regulations is effective because enzymes part of complex