Stimulation of pentose phosphate pathway dehydrogenase enzyme activities in ethionine-treated mice.
1. Mice treated with ethionine (intraperitoneally, 5mg./day for 4 days or 10mg./day for 3 days) showed a profound loss of hepatic glycogen, a decrease of glycogen synthetase activity, a development of hypoglycaemia, a two- to five-fold increase in the activity of glucose 6-phosphate dehydrogenase but no change in 6-phosphogluconate dehydrogenase and an earlier manifestation of the solubilization of phosphorylase as compared with glycogen synthetase. The administration of ATP did not prevent these effects. 2. During the early post-injection period (2-3 days) there was a further enhancement of the activity of glucose 6-phosphate dehydrogenase (tenfold) in the liver and a clear elevation of 6-phosphogluconate dehydrogenase activity (twofold). Subsequently, the glycogen concentration was restored, followed by an earlier reassociation of glycogen particle with phosphorylase than with glycogen synthetase, along with a disappearance of ethionine effect at about the eighteenth day. 3. Glucose 6-phosphate dehydrogenase from both control and ethionine-treated animals showed a marked preference for glucose 6-phosphate as substrate rather than for galactose 6-phosphate, whose rate of oxidation was only 10% of that of the glucose 6-phosphate. 4. Since actinomycin D, puromycin, 5-fluorouracil and dl-p-fluorophenylalanine failed to block the ethionine-enhanced glucose 6-phosphate dehydrogenase activity, the possibility that new enzyme protein synthesis is responsible for the effect is doubtful.
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001786:Blood Glucose; D003609:Dactinomycin / Q000494:pharmacology; D005001:Ethionine / Q000494:pharmacology*; D005472:Fluorouracil / Q000494:pharmacology; D005690:Galactose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism*; D005964:Glucosyltransferases / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis; D007003:Hypoglycemia / Q000139:chemically induced; D008112:Liver Glycogen / Q000378:metabolism; D051379:Mice; D010649:Phenylalanine / Q000494:pharmacology; D010734:Phosphogluconate Dehydrogenase / Q000378:metabolism*; D011691:Puromycin / Q000494:pharmacology; D013997:Time Factors
D000963:Antimetabolites; D001786:Blood Glucose; D008112:Liver Glycogen; D003609:Dactinomycin; D010649:Phenylalanine; D011691:Puromycin; D000255:Adenosine Triphosphate; D006003:Glycogen; D010734:Phosphogluconate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D005964:Glucosyltransferases; D005947:Glucose; D005472:Fluorouracil; D005001:Ethionine; D005690:Galactose