Down-regulation of the hexose transport system: metabolic basis studied with a fibroblast mutant lacking phosphoglucose isomerase.
Down-regulation ("curb") of hexose transport in Chinese hamster lung fibroblasts has been studied in a metabolic mutant highly defective in phosphoglucose isomerase (PGI; glucosephosphate isomerase; D-glucose-6-phosphate ketol-isomerase, EC 5.3.1.9). In the parental strain (PGI+) glucose as well as glucosamine and mannose were able to elicit a curb of the hexose transport system. In the PGI mutant, only glucose was able to mediate a transport curb. The inability of glucosamine and mannose to promote a transport curb in the PGI strain must be ascribed to the fact that the 6-esters of these aldohexoses are converted by their own specific deaminase and isomerase to fructose 6-phosphate, which initiates the pyruvate-tricarboxylate energy-yielding pathway but cannot be converted to glucose 6-phosphate in the mutant. The latter ester can be metabolized, but its metabolism in the mutant is confined to the pentose shunt. It is shown that inhibitors such as 2,4-dinitrophenol and malonate exert only slight inhibition of the pentose shunt yet release the glucose-mediated curb elicited by glucose and glucosamine in the parental PGI+ strain and also the glucose transport curb persisting in the PGI mutant.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D006224:Cricetinae; D004140:Dinitrophenols / Q000494:pharmacology; D004734:Energy Metabolism; D005944:Glucosamine / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology; D005956:Glucose-6-Phosphate Isomerase / Q000378:metabolism*; D006601:Hexoses / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008358:Mannose / Q000494:pharmacology; D010429:Pentoses / Q000378:metabolism
D004140:Dinitrophenols; D006601:Hexoses; D007773:Lactates; D010429:Pentoses; D019344:Lactic Acid; D005956:Glucose-6-Phosphate Isomerase; D005947:Glucose; D005944:Glucosamine; D008358:Mannose