Carbohydrate Metabolism in Leukocytes

In normal polymorphonuclear leukocytes the occurrence of a high rate of aerobic glycolysis with a concomitant large formation of lactic acid has been demonstrated (1, 2) and the enzymes and intermediates of the Embden-Meyerhof pathway have been isolated and identified (3-5). There are indications for the presence and activity of the Krebs cycle, but the contribution of this cycle to metabolism is very small when compared to that of the glycolytic pathway (6). Polymorphonuclear leukocytes contain glycogen and the enzymes involved in glycogenolysis are present (7). In previous work from this laboratory it was indicated that the carbons of acetate as traced by Cl4 label are incorporated into the glycogen of the leukocytes via the Krebs cycle (8). Pyruvate and iactate, however, followed a more direct path; probably involving the reversal of the pyruvic kinase reaction (8). In addition a highly asymmetrical distribution of label was observed in the glucose units of the glycogen, i.e. all 2and 3-carbon substrates, thus far tested, have yielded hexose units containing 80 to 90% of their labeling in carbon atoms 4, 5, and 6 (8). The occurrence of an active transaldolase exchange mechanism in leukocytes has been postulated to account for this distribution. A contribution of the pentose phosphate pathway to the metabolism of glucose by polymorphonuclear leukocytes has been demonstrated (9) and certain enzymes of this pathway have been characterized (10). Sbarra and Karnovsky (11) in their study of guinea pig polymorphonuclear leukocyte metabolism, noted a significantly higher ratio of C-l to C-6 of glucose oxidation to respiratory COs during phagocytosis than during the resting state. They concluded that the activity of the direct oxidative pathway was markedly stimulated by phagocytosis. However, Katz and Wood (12) have shown that the ratio of C-l to C-6 oxidation does not always provide a valid measure of the activity of the pentose cycle. In the present study the conversion of labeled ribose and xylose carbons to glycogen by leukocytes has been investigated. The labeling pattern observed in glycogen has been found to be consistent with the participation of the transketolase and transaldolase reactions in the formation of glycogen from these pentoses. -4 preliminary report of this work has been presented (13).