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

Increased activity of alcohol dehydrogenase

8%

(14/168)

Decreased activity of pyruvate dehydrogenase

55%

(93/168)

Decreased activity of lactate dehydrogenase

15%

(25/168)

Increased activity of isocitrate dehydrogenase

4%

(6/168)

Increased flux through the electron transport chain

12%

(20/168)

M 1 D

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