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Biochemistry Department, Upstate Medical Center, State University of New York, Syracuse, New York 13210
Oxamic acid did not inhibit oxygen utilization in intact cells or in an homogenate system of Sarcoma 37 ascites tumor cells when the concentration of inhibitor was 0.08 M or less. However, at higher concentrations of oxamate, it inhibited respiration. Lactic acid production was inhibited in the intact cells and homogenate system at concentrations of oxamate as low as 0.008 M. At a concentration of 0.08 M, lactate production decreased 80 percent in both systems. The oxidation of glucose-6-14C and glucose-1-14C to 14CO2 was depressed by oxamate in the homogenate system.
Pyruvate reduction to lactate was minimal in a nonglycolyzing homogenate system unless reduced diphosphopyridine nucleotide (DPNH) was added. However, oxamate had no effect on lactate production in this maximally fortified system. Data are presented to show that exogenous pyruvate was converted to lactate in the presence of DPNH and oxamate but that glycolysis was inhibited. An inhibiting effect of oxamate was shown to be at the hexokinase step.
The findings by Colowick and associates (8) that aerobic and anaerobic glycolysis are 100 times less sensitive to oxamate than is lactic dehydrogenase in intact Ehrlich ascites cells are not explained by assuming a semipermeable membrane.
1 This investigation was supported in part by USPHS Grant #CA-06194 from the National Cancer Institute, USPHS, and aided in part by Grant #P-143 from the American Cancer Society.
Received 12/26/67. Accepted 6/26/68.
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