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. 2013 Dec;33(12):1843-5.
doi: 10.1038/jcbfm.2013.168. Epub 2013 Sep 25.

Underestimation of the pentose-phosphate pathway in intact primary neurons as revealed by metabolic flux analysis

Patricia Rodriguez-Rodriguez  1 , Emilio Fernandez, Juan P Bolaños
Affiliations

Underestimation of the pentose-phosphate pathway in intact primary neurons as revealed by metabolic flux analysis

Patricia Rodriguez-Rodriguez et al. J Cereb Blood Flow Metab. 2013 Dec.

Abstract

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 VSports手机版. 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. .

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Figures

Figure 1
Figure 1
Glucose fluxes through glycolysis and pentose–phosphate pathway (PPP) in neurons. Incubation of rat cortical intact neurons in primary culture with dehydroepiandrosterone (DHEA) (1 μmol/L) increased by twofold the rate of glycolysis (A), the rate of PPP (B), and the concentrations of glucose-6-phosphate (G6P) (C); knockdown on phosphoglucose isomerase (PGI) increased by 1.8-fold the rate of PPP (D). The rates of glycolysis and PPP were determined as described in Methods. Data represent mean±s.e.m. values for three independent culture preparations. *P<0.05 (Student's t-test).
Figure 2
Figure 2
Pentose–phosphate pathway (PPP) is an important contributor to glucose consumption in neurons. Schematic representation of the main conclusion of this work, highlighting the critical contribution of phosphoglucose isomerase (PGI)–which converts PPP-derived F6P into glucose-6-phosphate (G6P)–to fueling PPP at the expense of G6P consumption through glycolysis. 6-Phosphofructo-1-kinase (PFK1), which converts fructose-6-phosphate (F6P) into fructose-1,6-bisphosphate (F16BP), is a ‘bottleneck' in neurons due to the low levels of fructose-2,6-bisphosphate (a positive effector of PFK1); this facilitates F6P conversion into G6P. Stoichiometry has been omitted for clarity, and dotted lines represent multiple reactions. GAP, glyceraldehyde-3-phosphate; PYR, pyruvate; R5P, ribulose-5-phosphate.
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