Week 4: pyruvate dehydrogenase

Question 1

Explain how pyruvate gets into the mitochondria

Answer 1

• The outer mitochondrial membrane is very porous and anything under 6000 Da can pass
• The inner mitochondrial membrane uses a H+ symporter which relies on the H+ gradient formed by the electron transport chain

Question 2

Describe the mitochondrial H+ gradient

Answer 2

[H+] is high outside the inner membrane

[H+] small inside the inner membrane

Question 3

what happens to pyruvate after it enters the mitochondria?

Answer 3

pyruvate needs to be converted into Acetyl-CoA

Pyruvate + NAD+ + CoASH -pyruvate dehydrogenase-> Acetyl-CoA + CO2 + NADH

Question 4

Describe the pyruvate dehydrogenase structure

Answer 4

3 complexes

E1 + E2 + E3 and cofactors

Cofactors

• TPP = Thiamine pyrophosphate (derived from vitamin B1)
• Lipoate
• FAD

Question 5

Vitamin B1 deficiency

Answer 5

fatigue because can’t generate ATP from lack of TPP cofactor

Question 6

Pyruvate dehydrogenase regulation

Answer 6

regulated by pyruvate kinase largely from product formation

• Pyruvate DH *active* + ATP -pyruvate kinase (kinase activity)-> Pyruvate DH *inactive* + ADP
  
  • High [Acetyl CoA] + activates kinase activity
  • High [NADH] + activates kinase activity
    
    • This is done because of the buildup of the product of pyruvate DH
• Pyruvate DH *inactive* -pyruvate kinase (phosphatase activity)-> Pyruvate DH *active* + Pi
  
  • High [Ca2+] activates the phosphatase activity and inhibits the kinase activity of pyruvate kinase (happenns from contraction events in muscle which releases Ca2+)
    
    • Ca2+ mediates the contraction event but also couples it to energy production

Question 7

Pyruvate dehydrogenase active form

Answer 7

dephosphorylated

Question 8

Pyruvate dehydrogenase inactive form

Answer 8

phosphorylated