Significance of Alternate Pathways in the Metabolism of Glucose

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Abstract
During the past 20 years the EMP-TCA (EMP=the Embden-Meyerhof-Parnas scheme of glycolytic cleavage; TCA=Krebs or tricarboxylic acid cycle) pathway of breakdown of sugar has come to be looked on as the main route for utilization of glucose. It is now clearly established that glucose is broken down by certain microorganisms by pathways other than the EMP pathway and remarkable progress is being made in detecting and elucidating these pathways. The situation in higher animals is less clearly defined. There is little doubt that there are pathways of metabolism differing from the EMP-TCA pathway and rapid strides are being made in determining the detailed mechanism of these pathways. Nevertheless the importance and exact role of these pathways in the over-all metabolism of the intact animal are not established. Hexose-monophosphate is an intermediate of both the EMP and the hexose-monophosphate oxidative pathways; therefore the occurrence of the alternate pathway should be reflected in the glycogen synthesized by the animal. As judged from the C14 pattern of the liver glycogen only a small portion of the total glucose metabolized by the rat traverses the hexosemonophosphate oxidative pathway. The calculations devised to assess the importance of alternate pathways involve many assumptions and uncertainties. Difficulties encountered in such a measurement are complex and it appears that results so far obtained must be interpreted with considerable caution. Labeled glucose appears to offer promise of providing some definite answers to these problems but refinements will almost certainly have to be made which include correction for differences in dilution which occur in the respective pathways. Determination of the relative role of different pathways in normal living cells is without doubt of the greatest fundamental importance to our understanding of life process and will in the future require more and more attention in all fields of metabolism. The complexity of the problem is increasingly evident as new pathways of metabolism are discovered.