MAGNITUDE OF MALATE-ASPARTATE REDUCED NICOTINAMIDE ADENINE-DINUCLEOTIDE SHUTTLE ACTIVITY IN INTACT RESPIRING TUMOR-CELLS

  • 1 January 1977
    • journal article
    • research article
    • Vol. 37  (11) , 4173-4181
Abstract
Measurements of respiration, CO2 and lactate production, and changes in the levels of various key metabolites of the glycolytic sequence and tricarboxylic acid cycle were made in 5 lines of rodent ascites tumor cells (2 strains of Ehrlich ascites mouse tumor cells, Krebs II carcinoma, AS-30D rat hepatoma and L1210 leukemia) incubated aerobically in the presence of uniformly labeled D-[14C]glucose. From these data, as well as earlier evidence demonstrating that the NADH shuttle in these cells requires a transaminase step and is identified as the malate-aspartate shuttle, metabolic flux diagrams were constructed for the 5 cell lines. These diagrams show the relative rates of glycolysis, tricarboxylic acid cycle, electron transport and the malate-aspartate shuttle in these tumors. Large amounts of cytosolic NADH were oxidized by the mitochondrial respiratory chain via the NADH shuttle, comprising anywhere from about 20-80% of the total flow of reducing equivalents to O2 in these tumors. Calculations of the sources of energy for ATP synthesis indicated that about 1/3 of the respiratory ATP is generated by electron flow originating from cytosolic NADH via the malate-aspartate shuttle.

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