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Evaluation of catabolic pathways of glucose in mammalian systems.

B. Bloom,M. R. Stetten,D. Stetten

Published 1953 in Journal of Biological Chemistry

ABSTRACT

Earlier studies from this laboratory have shown that free gluconic acid is extensively oxidized to COZ and converted in part to glucose by the intact rat. The production of free gluconic acid, however, could not be detected (I). The major pathway of gluconate catabolism involves decarboxylation at carbon atom 1 and utilization of the residue of the molecule for glucogenesis (2). Reduction of gluconate to glucose proved to be a very minor process. These findings are consistent with the view that gluconic acid, presumably after phosphorylation, enters that series of reactions referred to as the “oxidative” pathway of glucose utilization (3-5). The existence in many biological systems of such a pathway, which is distinct from that usually referred to as the glycolytic or Embden-Meyerhof scheme, has recently attracted much attention. This alternative ‘(oxidative” route, variously known as the Warburg-Dickens-Lipmann pathway or the “hexose monophosphate shunt” involves the intermediate occurrence of 6-phosphogluconate and presumably 3-keto-6-phosphogluconate, followed by decarboxylation, to yield CO* and 5-phosphoribulose (6). Clearly the sequence in which the several carbon atoms of glucose appear as COZ in a respiring system will be quite different if the “oxidative” rather than the glycolytic scheme is operative. In the hope of gaining information as to the occurrence and extent of a non-glycolytic pat,hway of glucose utilization in the intact mammal and in tissues derived from it, experiments have been performed in which the yields of C1402 from glucose-U-C14 and glucose-l-Cl4 have been compared.’ Intact rats, rat liver and kidney slices, and rat diaphragm sections have been studied in this regard. The glycolytic scheme yields, as intermediate products of glucose catabolism, 2 molecules of pyruvate or lactate in which carbon atoms 1, 2, and 3 correspond to glucose carbon atoms 3 and 4, 2 and 5, 1 and 6 respectively. Experiments parallel to those with glucose have therefore been carried out in each biological system with lactate-1-C14, lactate-2-C14, and lactate-3-C14

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