Oxidation of pyruvate, malate, citrate, and cytosolic reducing equivalents by AS-30D hepatoma mitochondria.
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.
Dietzen
D J
DJ
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis 46202.
Davis
E J
EJ
D000154:Aconitate Hydratase / Q000378:metabolism; D000818:Animals; D002951:Citrates / Q000378:metabolism*; D019343:Citric Acid; D002952:Citric Acid Cycle; D003600:Cytosol / Q000378:metabolism*; D004563:Electrochemistry; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D007700:Kinetics; D008114:Liver Neoplasms, Experimental / Q000201:enzymology* / Q000648:ultrastructure; D008291:Malate Dehydrogenase / Q000378:metabolism; D008293:Malates / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000201:enzymology*; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism*; D019289:Pyruvic Acid; D051381:Rats; D017207:Rats, Sprague-Dawley
D002951:Citrates; D005227:Fatty Acids; D008293:Malates; D011768:Pyruvate Dehydrogenase Complex; D011773:Pyruvates; D009243:NAD; D019343:Citric Acid; C030298:malic acid; D019289:Pyruvic Acid; D008291:Malate Dehydrogenase; D007521:Isocitrate Dehydrogenase; D000154:Aconitate Hydratase