Modulation of carbohydrate metabolism during carcinogenesis.

Investigations in a number of experimental models and some observations in humans have indicated that changes in carbohydrate metabolism precede the development of many tumor types and appear to be closely associated, if not causally related, to neoplastic cell transformation. Thus, a decrease or increase of many enzymes (including those of the carbohydrate metabolism) and/or a transient excessive storage of polysaccharides (glycogenosis, mucopolysaccharidosis) or lipids (lipidosis) was demonstrated by cytochemical and biochemical methods during carcinogenesis induced by chemicals in liver, pancreas, colon, kidney, and brain. The results suggest that an ordered pattern of metabolic and morphologic changes occurs during neoplastic cell transformation. Apparently, an increase in the flux of certain metabolic pathways such as the hexose-monophosphate shunt and glycolysis develops during transformation of many cell types. This metabolic aberration is conventionally explained as a consequence of a higher metabolic requirement. However, it is conceivable that during neoplastic cell transformation certain metabolites are accumulated in unphysiologically high concentrations (especially intermediates of glucose metabolism) and thereby force the cell to activate alternative metabolic pathways.