chapter 18 Pyruvate Dehydrogenase Complex

Flashcards about the pyruvate dehydrogenase complex.

Why is the reaction catalyzed by the pyruvate dehydrogenase complex crucial?

A crucial juncture in metabolism because it links glycolysis to the citric acid cycle.

How is the pyruvate dehydrogenase complex regulated?

Two mechanisms: phosphorylation/dephosphorylation and energy charge regulation.

What role does the pyruvate dehydrogenase complex play in linking glycolysis to the citric acid cycle?

It converts pyruvate into acetyl CoA, linking glycolysis to the citric acid cycle.

Under aerobic conditions, pyruvate enters the mitochondria where it is converted into what molecule?

Acetyl CoA

Acetyl CoA is the fuel for what cycle?

Citric acid cycle

Where does the oxidative decarboxylation of pyruvate take place?

The mitochondrial matrix.

What is the fuel of the citric acid cycle?

Acetyl CoA.

What are the three steps in the synthesis of acetyl CoA from pyruvate?

Decarboxylation, oxidation, and transfer to CoA.

In decarboxylation, what does pyruvate combine with?

Pyruvate combines with thiamine pyrophosphate (TPP).

TPP, a coenzyme, is derived from what?

Vitamin thiamine.

The hydroxyethyl group attached to TPP is oxidized to form an acetyl group while being simultaneously transferred to what molecule?

Lipoamide.

Lipoamide is formed by the attachment of what to a lysine residue?

Vitamin lipoic acid.

Which enzyme catalyzes the transfer of the acetyl group from acetyl-lipoamide to coenzyme A to form acetyl CoA?

E2.

Which enzyme catalyzes the reoxidation of dihydrolipoamide?

Dihydrolipoamide dehydrogenase (E3).

What term refers to the transfer of molecules between consecutive enzymes without equilibration?

Substrate channeling.

What are the two principal fates of acetyl CoA?

Acetyl CoA and fatty acids.

What phosphorylates and inactivates E1?

A kinase.

What removes the phosphate and activates E1?

A phosphatase.

What inhibits the pyruvate dehydrogenase complex?

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?

Increased efficiency, reduced loss of intermediates, enhanced regulation, protection from degradation, and compartmentalization.

What condition results from a phosphatase deficiency in the pyruvate dehydrogenase complex?

Lactic acidosis.

What kind of diet minimizes the need to metabolize glucose in patients with pyruvate dehydrogenase deficiencies?

Ketogenic diet.

What deficiency results in insufficient pyruvate dehydrogenase activity?

Thiamine deficiency.

What neuromuscular pathology is caused by insufficient pyruvate dehydrogenase activity?

Beriberi.

What inhibits pyruvate dehydrogenase complex activity by binding to dihydrolipoamide?

Mercury and arsenite.

What can counter the effects of arsenite poisoning?

2,3-Dimercaptopropanol.

What life-threatening condition results from a lack of adequate blood flow?

Shock.

What is the most common variety of shock?

Hypovolemic or hemorrhagic shock.

What inhibits the kinase associated with the pyruvate dehydrogenase complex and is used to treat shock?

Dichloroacetate (DCA).

What is the role of blood protein hemoglobin?

It carries O2 from the lungs to the tissues.

What process, requiring O2, generates 90% of the ATP that a typical tissue requires?

Cellular respiration.

In the absence of O2, what is the only means to generate ATP?

Lactic acid fermentation.

What is the function of the kinase associated with the pyruvate dehydrogenase complex?

It phosphorylates and inhibits the complex.

What does the lipoamide arm allow in the pyruvate dehydrogenase complex ?

Allows rapid movement of substrates and products from one active site of the complex to another

What is the specialized group of molecules also referred to as functionally linked reactions called?

Metabolons

What does Pyruvate dehydrogenase (PDH) kinase do ?

Phosphorylates and inactivates PDH

What does PDH phosphatase do ?

Activates the dehydrogenase by removing the phosphoryl group

What do Mercury and arsenite bind to ?

The two sulfurs of the dihydrolipoamide

What does PDH deficiency result in?

Elevated levels of lactate and pyruvate