Stimulation of pentose phosphate pathway dehydrogenase enzyme activities in ethionine-treated mice

Abstract

Mice treated with ethionine (intraperitoneally, 5 mg per day for 4 days or 10 mg per day for 3 days) showed a profound loss of hepatic glycogen, a decrease of glycogen synthetase activity, a development of hypoglycemia, a 2 - to 5 -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. During the early post-injection period (2-3 days) there was a further enhancement of the activity of glucose 6-phosphate dehydrogenase (10-fold) in the liver and a clear elevation of 6-phosphogluconate dehydrogenase activity (2-fold). 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 18th day. 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. Since actinomy-cin 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.