Chapter 12: The Pyruvate Dehydrogenase (PDH) Complex

Question 1

Cytoplasmic pyruvate

Answer 1

• Must enter the mitochondria

Question 2

Metabolism converges on

Answer 2

• The pyruvate dehydrogenate complex

Question 3

Control of pyruvate dehydrogenase activity

Answer 3

• Inactivation by phosphorylation (eukaryotes only)
• Activation by dephosphorylation
• Allosteric control

Question 4

PDH multienzyme complex

Answer 4

• Three non-covalently linked enzymes
• Two regulatory enzymes (kinase and phosphatase)
• Five cofactors

Question 5

Three non-covalently linked enzymes of PDH complex

Answer 5

• Pyruvate dehydrogenase (E1)
• Lipoate acetyltransacetylase (E2)
• Lipoamide dehydrogenade (E3)

Question 6

Five cofactors of PDH complex

Answer 6

• Thiamine pyrophosphate (thiamine = Vitamin B1)
• Lipoic acid
• Flavin adenine dinucleotide
• Coenzyme-A (CoA-SH)
• NAD+

Question 7

Thiamine pyrophosphate (TPP)

Answer 7

• Decarboxylates pyruvate

- Yields a hydroxyethyl-TPP carbanion

Question 8

Lipoic acid

Answer 8

• Accepts the hydroxoethyl carbanion from TPP as an acetyl group

Question 9

Coenzyme-A (CoA)

Answer 9

• Accepts the acetyl group from lipoamide

Question 10

Flavin adenine dinucleotide (FAD)

Answer 10

• Reduced by lipoamide

Question 11

Nicotinamide adenine dinuleotide (NAD+)

Answer 11

• Reduced by FADH2

Question 12

Oxidative decarboxylation of pyruvate catalyzed by

Answer 12

• Pyruvate dehydrogenase

Question 13

Pyruvate translocase

Answer 13

• Helps pyruvate across the inner mitochondrial membrane

Question 14

Pyruvate that is not phosphorylated can pass through membrane

Answer 14

• By diffusion

- Using a specific translocase

Question 15

Overall PDH Reaction

Answer 15

1. Oxidative decarboxylation
2. Pyruvate is oxidized > forms Acetyl-SCoA and O2
3. NAD+ is reduced to form NADH and H+

Question 16

Reaction mechanism of PDH complex

Answer 16

1. Decarboxylation of pyruvate
2. Oxidation of hydroxyethyl TPP
3. Acetyl-SCoA formation
4. Oxidation of lipoamide

Question 17

2 different fates of pyruvate in metabolism

Answer 17

• Converted to Acetyl-CoA

- Used as a substrate for gluconeogenesis

Question 18

Options when pyruvate’s fate is conversion to Acetyl-CoA

Answer 18

• Enter CAC > degraded and production of energy

- Used in fatty acid biosynthesis

Question 19

Purpose of pyruvate when it becomes a substrate for gluconeogenesis

Answer 19

• Used for the synthesis and storage of glycogen

Question 20

PDH step is irreversible

Answer 20

• Commits carbon atoms of glucose to CAC or FA synthesis

Question 21

Acetyl-SCoA (breakdown product of fatty acids)

Answer 21

• Cannot be used in gluconeogenesis because pyruvate is irreversible

Question 22

Oxaloacetate can be used to

Answer 22

• Make glucose during starvation

Question 23

Turns on the PDH complex

Answer 23

• Dephosphorylation

Question 24

Covalent phosphorylation at 3 serine residues inhibits

Answer 24

• The PDH complex

Question 25

Mg++ dependent kinase

Answer 25

- In mammals not prokaryotes - Stimulated by ATP, acetyl-SCoA, and NADH - Inhibited by pyruvate and ADP

Question 26

Activation by dephosphorylation

Answer 26

- Ca++ dependent phosphatase | - Favored by insulin in fed state

Question 27

Allosteric inhibition of PDH complex by

Answer 27

- ATP - NADH (product) - Acetyl-SCoA (product)

Question 28

High levels of product

Answer 28

- Inhibit PDH | - Promote phosphorylation

Question 29

High levels of substrate

Answer 29

- Stimulate PDH | - Inhibit phosphorylation

Question 30

When insulin activates a PDH phosphatase

Answer 30

- Increases PDH activity

Question 31

Covalent modification of eukaryotic pyruvate dehydrogenase

Answer 31

- Specific phosphorylation of serine residues on E1

Question 32

Thiamine deficiency/Beriberi (pyruvate oxidation disorder)

Answer 32

- Cofactors not available - Involves vitamin B1 - Neurological symptoms: limb paralysis, cardiac insufficiency, and enlarged heart

Question 33

Arsenic or mercuric poisoning (pyruvate oxidation disorder)

Answer 33

- Cofactors are disabled | - Prokaryotic enzyme more sensitive

Question 34

Genetic diseases

Answer 34

- May cause PDH to be absent or defective - Lactate acidosis - Ataxia, lethargy, poor visual tracking, and tachycardia

Question 35

Arsenic poisoning

Answer 35

- Arsenite and organic arsenical bind to sulfhydryl compounds - Lipoamide containing enzymes include PDH and alpha-ketoglutarate dehydrogenase & glyceraldehyde-3-P dehydrogenase - Uncouples oxidative phosphorylation - More toxic to microbes

Question 36

Allosteric activation of PDH complex by

Answer 36

- AMP - CoA - NAD+

Question 37

Oxidative decarboxylation of pyruvate occurs in

Answer 37

- The mitochondrial matrix

Question 38

Major, but not only source of Acetyl-SCoA

Answer 38

- Oxidative decarboxylation of pyruvate