6-Aminonicotinamidee inhibition of the pentose phosphate pathway in rat neocortex

6-Aminonicotinamide (6-AN) is thought to inhibit the pentose phosphate path way (PPP) since large increases in 6-phosphogluconate are observed followin g its administration. Immediately following 45 min i.v. infusion of [2-C-13 ]glucose to controls and 6-AN-treated (50 mg/kg i.p. given 4h previously) S prague-Dawley rats (n = 5 for both groups), metabolism was arrested using f reeze-funnel fixation. Chloroform-methanol-water neocortical extracts from animals administered with 6-AN demonstrated elevated levels of 6-phosphoglu conate and 6-phosphoglucono-delta-lactone, both of which demonstrated label ing through metabolism of [2-C-13]glucose. Comparison of the C-2 and C-3 la ctate positions using H-1 NMR spectroscopy showed that the fraction of gluc ose metabolized through the PPP is unchanged by 6-AN (14 +/- 0.6% vs 14 +/- 0.3% in control animals). It is hypothesized that as the PPP is inhibited by metabolites of 6-AN in the neocortex, glycolysis is inhibited in a propo rtionate manner through an inhibitory effect on phosphoglucose isomerase by 6-phosphogluconate and/or 6-phosphoglucono-delta-lactone. NeuroReport 11:1 845-1848 (C) 2000 Lippincott Williams & Wilkins.