Underestimation of the pentose-phosphate pathway in intact primary neurons as revealed by metabolic flux analysis.
The rates of glucose oxidized at glycolysis and pentose-phosphate pathway (PPP) in neurons are controversial. Using [3-(3)H]-, [1-(14)C]-, and [6-(14)C]glucose to estimate fluxes through these pathways in resting, intact rat cortical primary neurons, we found that the rate of glucose oxidized through PPP was, apparently, ∼14% of total glucose metabolized. However, inhibition of PPP rate-limiting step, glucose-6-phosphate (G6P) dehydrogenase, increased approximately twofold the glycolytic rate; and, knockdown of phosphoglucose isomerase increased ∼1.8-fold the PPP rate. Thus, in neurons, a considerable fraction of fructose-6-phosphate returning from the PPP contributes to the G6P pool that re-enters PPP, largely underestimating its flux.
Institute of Functional Biology and Genomics (IBFG), University of Salamanca-CSIC, Salamanca, Spain.
Patricia
P
Rodriguez-Rodriguez
Emilio
E
Fernandez
Juan P
JP
Bolaños
D000818:Animals; D002247:Carbon Isotopes / Q000378:metabolism; D002478:Cells, Cultured; D005636:Fructosephosphates / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006019:Glycolysis; D064688:Metabolic Flux Analysis; D009474:Neurons / Q000378:metabolism*; D010427:Pentose Phosphate Pathway; D051381:Rats; D017208:Rats, Wistar
D002247:Carbon Isotopes; D005636:Fructosephosphates; C027618:fructose-6-phosphate; D005947:Glucose