Reciprocal effects of 2-fluoro-2-deoxy-D-glucose and glucose on their metabolism in Saccharomyces cerevisiae studied by multi-nuclear NMR spectroscopy.
The effects of various concentrations of 2-fluoro-2-deoxy-D-glucose (FDG) on the aerobic metabolism of glucose and the reciprocal effect of glucose on the metabolism of FDG in glucose-grown repressed Saccharomyces cerevisiae cells were studied at 30 degrees C in a standard pyrophosphate medium containing 5 x 10(7) cells/ml by 1H-, 19F-, 31P-NMR and biochemical techniques. The glucose consumption rate is reduced by about 57% and 71% in the presence of 5 mM FDG and 10 mM FDG respectively. Under the same conditions, the ethanol production rate also decreases about 54% and 68%, respectively. When FDG is the unique carbon source, the alpha- and beta-anomers of 2-fluoro-2-deoxy-D-glucose-6-phosphate (FDG6P) and a much smaller quantity of 2-fluoro-2-deoxy-gluconic acid (FDGA) were observed. The quantities of alpha- and beta-FDG6P reach their maximum values within 1 h of incubation and then decrease continuously. In contrast, Glc favors the consumption of FDG and the synthesis of FDG6P and uridine-5'-diphosphate fluorodeoxy-glucose (UDP-FDG). In the presence of Glc, FDG6P reaches a plateau after 1 h or 2 h of incubation while UDP-FDG increases regularly with time. Apart from trehalose, no other disaccharide such as fluoro-dideoxy-trehalose (FDG-FDG) or fluoro-deoxy-trehalose (FDG-Glc) were observed. Thus, in contrast to UDP-Glc, UDP-DG, Glc6P and DG6P, UDP-FDG and FDG6P are not good substrates for trehalose-6-P synthetase.(ABSTRACT TRUNCATED AT 250 WORDS)
Tran-Dinh
S
S
Département de Biologie Cellulaire et Moléculaire, CEA, CE Saclay, Gif-sur-Yvette, France.
Courtois
A
A
Wietzerbin
J
J
Bouet
F
F
Herve
M
M
D002455:Cell Division / Q000187:drug effects; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000378:metabolism*
D005462:Fluorine Radioisotopes; D019788:Fluorodeoxyglucose F18; D003847:Deoxyglucose; D005947:Glucose