US EPA

1024133 

Journal Article 

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

Tyson, RL; Perron, J; Sutherland, GR 

2000 

1 

NeuroReport
ISSN: 0959-4965
EISSN: 1473-558X 

11 

9 

1845-1848 

English 

10884030 

10.1097/00001756-200006260-00009 

WOS:000087759800014 

6-Aminonicotinamide (6-AN) is thought to inhibit the pentose phosphate pathway (PPP) since large increases in 6-phosphogluconate are observed following its administration. Immediately following 45 min i.v. infusion of [2-(13)C]glucose to controls and 6-AN-treated (50 mg/kg i.p. given 4 h previously) Sprague-Dawley rats (n = 5 for both groups), metabolism was arrested using freeze-funnel fixation. Chloroform-methanol-water neocortical extracts from animals administered with 6-AN demonstrated elevated levels of 6-phosphogluconate and 6-phosphoglucono-delta-lactone, both of which demonstrated labeling through metabolism of [2-(13)C]glucose. Comparison of the C-2 and C-3 lactate positions using 1H NMR spectroscopy showed that the fraction of glucose 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 proportionate manner through an inhibitory effect on phosphoglucose isomerase by 6-phosphogluconate and/or 6-phosphoglucono-delta-lactone. 

6-Aminonicotinaamide; glucose metabolism; nuclear magnetic resonance spectroscopy; pentose phosphate pathway