Updated: 8/23/2017

Pyruvate Dehydrogenase Complex

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Introduction
  • Function
    • catalyze conversion of pyruvate to acetyl-CoA
    • net reaction
      • pyruvate + NAD+ + CoA → acetyl-CoA + CO2 + NADH
    • irreversible
  • Structure
    • 3 enzymes that require 5 cofactors
      • thiamine pyrophosphate (B1)
      • FAD (B2)
      • NAD (B3)
      • CoA (B5)
      • lipoic acid
    • similar to α-ketoglutarate dehydrogenase complex
  • Regulation
    • activators of pyruvate dehydrogenase
      • ↓ in energy status of the cell
        • ↑ NAD+/NADH ratio
        • ↑ ADP
      • ↑ exercise
      • ↑ Ca2+
      • ↑ insulin
    • inhibited by acetyl-CoA
  • Clinical relevance
    • pyruvate dehydrogenase deficiency 
      • pathophysiology
        • X-linked (variable penetrance in females)
        • accumulation of
          • pyruvate
          • alanine
        • lactic acidosis
          • pyruvate shunted to lactate to regenerate NAD+ 
      • presentation
        • neurological defects
      • treatment
        • ↑ ketogenic nutrients
          • lysine and leucine 
    • arsenic poisoning
      • inhibits pyruvate dehydrogenase
        • via inhibition of lipoic acid
      • presentation
        • vomiting
        • rice water stools
        • garlic breath

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(M1.BC.14.34) A 64-year-old man who is post-op day 4 following a radical nephrectomy is noted to have a temperature of 103.4F, pulse of 115, blood pressure of 86/44, and respiratory rate of 26. Arterial blood gas shows a pH of 7.29 and pCO2 of 28. Chemistry panel shows: Na+ 136, Cl- 100, HCO3- 14. CBC is significant for a significant leukocytosis with bandemia. The laboratory reports that blood cultures are growing gram positive cocci.

Which of the following is true about this patient's biochemical state?

QID: 100099
1

Increased activity of alcohol dehydrogenase

4%

(2/52)

2

Decreased activity of pyruvate dehydrogenase

63%

(33/52)

3

Decreased activity of lactate dehydrogenase

19%

(10/52)

4

Increased activity of isocitrate dehydrogenase

6%

(3/52)

5

Increased flux through the electron transport chain

2%

(1/52)

M 1 D

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