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The Aerobic Carbohydrate Metabolism of Leukocytes in Health and Leukemia II. The Effect of Various Substrates and Coenzymes on Glycolysis and Respiration^*

( Atomic Energy Project and the Department of Medicine, School of Medicine, University of California at Los Angeles, Los Angeles, Calif.)

Data have been presented on the oxygen consumption, glucose utilization, and lactic acid production of homogenates of leukocytes isolated from normal (N), chronic myelocytic (CML), and chronic lymphatic leukemic (CLL) blood. Studies were made of the effect of the following substrates in varying combinations: glucose, hexose diphosphate, pyruvate, and succinate. Effects of varying added DPN, DPNH₂, ATP, and cytochrome c were also studied. Data were expressed per 10¹⁰ cells.

Although leukocytes have a predominantly aerobic glycolytic metabolism, the relative preponderance of aerobic glycolysis over respiration depends strictly on the availability of glycolyzable substrates. The glycolysis to respiration ratio is much higher when glucose is present than when it is absent. Of the three tissues, CLL homogenates have the lowest ratio of glycolysis to respiration.

Qualitative as well as quantitative differences in metabolic performance occur on manipulation of substrates. Succinate stimulates oxygen uptake to a greater extent in N than in leukemic material. With pyruvate as the substrate, and with DPN present, lactic acid production is low unless glucose is added.

Omission or manipulation of added cofactors profoundly affected metabolic rates. N, CML, and CLL homogenates required added ATP, DPN, and cytochrome c for maximal activity. Leukemic leukocytes had a greater cytochrome c requirement for maximal oxygen uptake than N cells. CLL homogenates had a greater than normal DPN requirement for maximal lactic acid production. Normal cells showed a greater lability to cofactor manipulation in their oxygen and glucose consumption, while leukemic cells were most variable in their lactic acid production.

^* Based on work performed under Contract No. AT-04-1-GEN-12 between the Atomic Energy Commission and the University of California at Los Angeles.

Received 6/26/52.

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