Inhibition of 6-phosphogluconate dehydrogenase by glucose 1,6-diphosphate in human normal and malignant colon extracts.
Increased activity of 6-phosphogluconate dehydrogenase was found in human colon tumors as compared to the adjacent unaffected mucosa. Glucose 1,6-diphosphate (Glc-1,6-P2), an endogenous potent regulator of glucose metabolism, markedly inhibited the activity of 6-phosphogluconate dehydrogenase (6-PGD) in extracts of the normal and malignant human colon. Glc-1,6-P2 also inhibited the activity of hexokinase in these extracts. The endogenous levels of Glc-1,6-P2 in the colon and tumors were measured. Since the pentose cycle can be inhibited by Glc-1,6-P2, means to increase endogenous levels of Glc-1,6-P2 or to introduce it into cells, might result in antitumor effects.
D003110:Colonic Neoplasms / Q000201:enzymology*; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives*; D005958:Glucosephosphates / Q000032:analysis / Q000494:pharmacology*; D006593:Hexokinase / Q000037:antagonists & inhibitors; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000201:enzymology; D010429:Pentoses / Q000378:metabolism; D010732:Phosphofructokinase-1 / Q000378:metabolism; D010734:Phosphogluconate Dehydrogenase / Q000037:antagonists & inhibitors*; D012267:Ribosemonophosphates / Q000096:biosynthesis
D005958:Glucosephosphates; D010429:Pentoses; D012267:Ribosemonophosphates; C031626:ribose-5-phosphate; D019298:Glucose-6-Phosphate; C016473:glucose-1,6-bisphosphate; D010734:Phosphogluconate Dehydrogenase; D006593:Hexokinase; D010732:Phosphofructokinase-1