Abstract:
: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.
journal_name
Neuroreportjournal_title
Neuroreportauthors
Tyson RL,Perron J,Sutherland GRdoi
10.1097/00001756-200006260-00009subject
Has Abstractpub_date
2000-06-26 00:00:00pages
1845-8issue
9eissn
0959-4965issn
1473-558Xjournal_volume
11pub_type
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