Oxidation of pyruvate, malate, citrate, and cytosolic reducing equivalents by AS-30D hepatoma mitochondria

Arch Biochem Biophys. 1993 Aug 15;305(1):91-102. doi: 10.1006/abbi.1993.1397.


Mitochondria isolated from normal rat liver and AS-30D hepatoma were concurrently evaluated with regard to their bioenergetic and metabolic properties. AS-30D mitochondria oxidized many NAD-linked respiratory substrates at rates 1.5-4 times faster than those from liver, a fact which contributes to their diminished membrane depolarization on conversion from state 4 to state 3 respiration. AS-30D mitochondria exhibited no signs of a "truncated" Krebs cycle, nor did they oxidize malate preferentially based upon its origin in the cytosol or the mitochondrial matrix. In addition, beta-oxidation in AS-30D mitochondria was not sufficient to suppress respiratory CO2 production and induce pyruvate carboxylation to the extent observed in liver. Finally, AS-30D mitochondria were able to oxidize externally generated NADH in a reconstituted system, but in a manner independent of the transmembrane electrical potential (delta psi), suggesting that the malate-aspartate shuttle is not operable in vivo. This fact may necessitate the adaptations tumor cells make to reoxidize cytosolic NADH through glycolysis even in the presence of adequate oxygen.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aconitate Hydratase / metabolism
  • Animals
  • Citrates / metabolism*
  • Citric Acid
  • Citric Acid Cycle
  • Cytosol / metabolism*
  • Electrochemistry
  • Fatty Acids / metabolism
  • Female
  • Isocitrate Dehydrogenase / metabolism
  • Kinetics
  • Liver Neoplasms, Experimental / enzymology*
  • Liver Neoplasms, Experimental / ultrastructure
  • Malate Dehydrogenase / metabolism
  • Malates / metabolism*
  • Mitochondria, Liver / enzymology*
  • NAD / metabolism
  • Oxidation-Reduction
  • Pyruvate Dehydrogenase Complex / metabolism
  • Pyruvates / metabolism*
  • Pyruvic Acid
  • Rats
  • Rats, Sprague-Dawley


  • Citrates
  • Fatty Acids
  • Malates
  • Pyruvate Dehydrogenase Complex
  • Pyruvates
  • NAD
  • Citric Acid
  • malic acid
  • Pyruvic Acid
  • Malate Dehydrogenase
  • Isocitrate Dehydrogenase
  • Aconitate Hydratase