Decreased labeling of amino acids by inhibition of the utilization of [3H, 14C]glucose via the hexosemonophosphate shunt in rat brain in vivo.
Treatment of rats with 6-aminonicotinamide showed a small but significant decrease in the labeling of amino acids in the brain after injection of [3H]acetate. The results of these experiments also gave evidence of the presence of [3H]glucose and [3H]acetate, and an increase in [3H]glucose content in the brain of 6-aminonicotinamide treated rats. To apportion the contribution of [3H]glucose formed by gluconeogenesis from [3H]acetate to the labeling of amino acids a method was formulated based on the measurement of radioactivity of amino acids, lactate and free sugars in brain after injection of [6-3H]glucose or [1-3H]glucose relative to that after co-injection of [U-14C]glucose or [2-14C]glucose. In contrast to the expected formation of [1,6-3H]glucose by gluconeogenesis from [3H]acetate, 3H-labeled glucose isolated from brain, blood and liver showed the presence of [6-3H]glucose only. The values corrected for the presence of [6-3H]glucose showed that treatment with 6-aminonicotinamide had no effect on the labeling of amino acids by oxidation of [3H]acetate. These findings indicated that a significant decrease in the labeling of amino acids from [U-14C]glucose reported previously and again confirmed using [1-3H], [6-3H], [2-14C] or [U-14C]glucose in the present investigation was not due to the inhibition of the activities of enzymes of the citric acid cycle. These results support the postulated role of the hexosemonophosphate shunt for the utilization of glucose in providing neurotransmitter amino acids glutamate and gamma-aminobutyrate.
D000085:Acetates / Q000378:metabolism; D019342:Acetic Acid; D000596:Amino Acids / Q000096:biosynthesis*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes; D005947:Glucose / Q000378:metabolism*; D006600:Hexosephosphates / Q000378:metabolism*; D008297:Male; D011865:Radioisotope Dilution Technique; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium
D000085:Acetates; D000596:Amino Acids; D002250:Carbon Radioisotopes; D006600:Hexosephosphates; D014316:Tritium; D005947:Glucose; D019342:Acetic Acid