Control of sugar transport in human fibroblasts independent of glucose metabolism or carrier-substrate interaction.
Transport regulation by different metabolizable and nonmetabolizable sugars was studied in human fibroblasts. Sugars were classed as glucose-like (D-mannose, 3-0-methyl-D-glucose, thio-D-glucose, and D-allose) and starvation-like (D-galactose, D-fructose, L-glucose, D-xylose, 6-deoxy-D-glucose and 2-deoxy-D-glucose) based on their competence in curbing glucose starvation enhanced transport. No significant correlation existed between the ability of a sugar to curb hexose transport and the KI of that sugar in inhibiting hexose transport. Independence of the transport curb from glucose metabolism was observed since nonmetabolizable analogs of D-glucose when substituted for D-glucose in the culture medium effected glucose [i.e. 3-0-methyl-D-glucose (3-OMG)] and starvation-like (i.e. 6- and 2-deoxy-D-glucose) effects. The KI of inhibition pf 2-deoxy-D-glucose transport for 3-OMG was 8.5 mM, similar to those obtained for 6-deoxyglucose and 2-deoxyglucose on 2-deoxyglycose transport (7.5 and 3.5 mM, respectively) and on 3-0-methylglucose transport (3.5 and 2.5 mM, respectively). An equimolar mixture of D-glucose and 3-OMG (5.55 mM each) was more effective than 11.1 mM D-glucose or 3-OMG alone in curbing hexose transport or reversing hexose starvation induced increases in transport. The effect of 3-OMG may be independent of glucose metabolism but it is possible that 3-OMG structurally mimics a metabolite of glucose that may interact with intracellular regulators of carrier degradation and or expression.
D019325:3-O-Methylglucose; D001693:Biological Transport, Active / Q000187:drug effects; D050260:Carbohydrate Metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008757:Methylglucosides / Q000378:metabolism / Q000494:pharmacology; D009004:Monosaccharide Transport Proteins
D002352:Carrier Proteins; D008757:Methylglucosides; D009004:Monosaccharide Transport Proteins; D019325:3-O-Methylglucose; D003847:Deoxyglucose; D005947:Glucose