Pyruvate Dehydrogenase

 

Diagram of reaction:

 

 

Pyruvate dehydrogenase catalyzes the conversion of pyruvate into acetyl-CoA through oxidative decarboxylation.  The carboxyl group of pyruvate leaves the molecule as CO2 and the remaining two carbons become acetyl-CoA.

 

It is highly exergonic and can not be reversed in vivo.  ∆Go’ = -33.5 kJ/mol

 

Inhibitors

Activators

Responses to hormone signals

Acetyl-CoA (acts on E2 and activates pyruvate dehydrogenase kinase)

CoA-SH (acts on E2)

Insulin leads to inactivation of pyruvate dehydrogenase kinase, activating pyruvate dehydrogenase1

ATP (acts on complex, regulated via Mg2+/Ca2+ ratios)

AMP (acts on complex)

 

NADH (acts on E3 and activates pyruvate dehydrogenase kinase)

NAD+ (acts on E3)

 

Phosphorylation of E1 (through pyruvate dehydrogenase kinase)

Dephosphorylation of E1

 

 

Major metabolic role:  To regulate the formation of acetyl-CoA and its entrance into the citric acid cycle, depending on body energy needs for ATP. 

 

Structural information: 

  • Three enzymes: pyruvate dehydrogenase (E1); dihydrolipoamide transacetylase (E2); and dihydrolipoamide dehydrogenase (E3)
  • Pyruvate dehydrogenase (E1): 24 chains; linked to coenzyme thiamine pyrophosphate (TPP)
  • Dihydrolipoamide transacetylase (E2): 24 chains; contains tightly bound lipoic acid
  • Dihydrolipoamide dehydrogenase (E3): 12 chains; contains flavin adenine dinucleotide (FAD)
  • Five coenzymes (includes NAD+ and coenzymeA which appear in the overall reaction, as well as thiamine pyrophosphate, lipoic acid, and flavin adenine dinucleotide – attached to E1, E2, and E3 respectively)
  • Total size: 4.6 million – 9.2 million Daltons, depending on the organism.

 

Additional diagram of Pyruvate Dehydrogenase Reaction – illustrating Pathway and Coenzymes.

 

All Figures from:  Mathwes CK, van Holde KE, Ahern KG.  Biochemistry, Third Edition.  (2000) Addison, Wesley, Longman, Inc.,  San Francisco.

1Denton RM, McCormack JG, Rutter GA, Burnett P, Edgell NJ, Moule SK, Diggle TA.  The hormonal regulation of pyruvate dehydrogenase complex.  Adv Enzyme Regul. 1996: 36:183-98.