Derepression and carrier turnover: evidence for two distinct mechanisms of hexose transport regulation in animal cells.
Hexose uptake by hamster cells was increased five to ten fold by either substituting D-fructose for glucose or by completely omitting D-glucose from the culture medium for 24 to 48 hours. Conversely, when cycloheximide was present for 24 hours in media containing glucose, up to 20-fold decreases in hexose uptake were observed. However, these decreases in uptake activity were only observed over a narrow range of cycloheximide concentrations. After extended exposure to low concentrations of cycloheximide (0.05 to 10 mug/ml), the uptake by the fed cells decreased parallel with inhibition of protein synthesis whereas at high concentrations (greater than 50 mug/ml) uptake was increased. Cells deprived of glucose and maintained in the presence of cycloheximide did not show decreases in uptake activity. In separate experiments the high uptake rates of glucose-starved cells could be decreased by addition of glucose-free medium. The reversal was complete in 6 to 8 hours. The analog of glucose, 2-deoxy-D-glucose, did not promote the time-dependent decrease suggesting that the 6-phosphoester of glucose is not an inhibitor of transport. In addition, when cycloheximide is added at the same time as glucose, there is no decrease in uptake for at least 12 hours. We propose that turnover of components of hexose uptake systems could account for part of the control of hexose transport. Moreover, the results indicate that the turnover mechanism becomes inactive during glucose starvation and must be resynthetized following refeeding of the starved cells with glucose.
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured / Q000378:metabolism*; D006224:Cricetinae; D003513:Cycloheximide / Q000494:pharmacology; D003847:Deoxyglucose / Q000378:metabolism; D004794:Enzyme Repression; D005632:Fructose / Q000378:metabolism; D005690:Galactose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006601:Hexoses / Q000378:metabolism*; D008757:Methylglucosides / Q000378:metabolism; D010770:Phosphotransferases / Q000378:metabolism*; D014176:Protein Biosynthesis
D000596:Amino Acids; D006601:Hexoses; D008757:Methylglucosides; D005632:Fructose; D003513:Cycloheximide; D003847:Deoxyglucose; D010770:Phosphotransferases; D005947:Glucose; D005690:Galactose