Mitochondria, hexokinase and pyruvate kinase isozymes in the aerobic glycolysis of tumor cells.
At 9 mM glucose, experimental results show that mitochondrial phosphate depletion (induced by glucose phosphorylation, catalyzed by mitochondrial hexokinase) reduces the activities of the respiratory chain, oxidative phosphorylation, and glutaminase. Consequently, the 14C-lactate oxidation to 14CO2 is lowered in the presence of glucose. The fall of ATP level triggers a high aerobic glycolysis by deinhibiting fructose-6-P kinase. NADH, generated by enhanced glyceraldehyde-3-P dehydrogenase activity, increases the reducing power. Moreover, the lactate dehydrogenase (LDH) system is shifted toward lactate formation, while NAD+ is regenerated and the oligomycin-inhibited ATP production is replaced by the iodoacetate-inhibited ATP production. From 14CO2 production and lactate accumulation it is calculated that about 60% of 14C-glucose which disappears is channelled into extraglycolytic reactions. On the contrary, 82% of glucose below l mM is metabolized through non-glycolytic reactions. The pyruvate kinase-M2 (PK-M2) inhibition does not limit the glycolytic flow from 9 mM glucose, but it may cause sustained gluconeogenesis.
Petrucci
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Department of Basic and Applied Biology, University of L'Aquila, Italy.
Cesare
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Colafarina
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D000255:Adenosine Triphosphate / Q000378:metabolism / Q000494:pharmacology; D000332:Aerobiosis; D000409:Alanine / Q000494:pharmacology; D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002286:Carcinoma, Ehrlich Tumor / Q000201:enzymology* / Q000648:ultrastructure; D005260:Female; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D006019:Glycolysis; D006593:Hexokinase / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D019344:Lactic Acid / Q000378:metabolism; D051379:Mice; D008928:Mitochondria / Q000201:enzymology*; D010084:Oxidation-Reduction; D010710:Phosphates / Q000378:metabolism; D011770:Pyruvate Kinase / Q000378:metabolism*
D007527:Isoenzymes; D010710:Phosphates; D002245:Carbon Dioxide; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D006593:Hexokinase; D011770:Pyruvate Kinase; D005947:Glucose; D000409:Alanine