Hexose uptake regulation mediated through aerobic pathways: schism in a fibroblast mutant

A protracted type of down-regulation of the hexose transport system in cultured fibroblasts that depends on one main factor in their nutritional state, the presence or absence of metabolizable D- aldohexoses in the culture fluid, is discussed. Fructose feeding is unable to elicit a down-regulation, whereas mannose and D-glucosamine, regulation of the transport system. This down-regulation or transport curb depends on oxidative energy metabolism, because inhibitors of this type of metabolism bring about a striking release of the transport curb. Studies with a fibroblast mutant that lacks the enzyme glucosephosphate isomerase (D-glucose-6-phosphate ketol-isomerase, EC 5.3.1.9, abbreviated phosphoglucose isomerase) (pgi-) have indicated that two types of metabolism are needed: 1) oxidative energy metabolism, which in the pgi- mutant can still be generated effectively from L-glutamine or, in its absence, from mannose or D-glucosamine; 2) glucose-6-phosphate metabolism, either its catabolism through the pentose shunt or through the anabolic pathway to UDP glucose and UDP galactose. The schism in carbohydrate metabolism in the pgi- fibroblasts is clearly reflected through the development of the metabolically mediated curb of the hexose transport or uptake system.