The pentose phosphate pathway of glucose metabolism. Hormonal and dietary control of the oxidative and non-oxidative reactions of the cycle in liver.
1. Measurements were made of the non-oxidative reactions of the pentose phosphate cycle in liver (transketolase, transaldolase, ribulose 5-phosphate epimerase and ribose 5-phosphate isomerase activities) in a variety of hormonal and nutritional conditions. In addition, glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase activities were measured for comparison with the oxidative reactions of the cycle; hexokinase, glucokinase and phosphoglucose isomerase activities were also included. Starvation for 2 days caused significant lowering of activity of all the enzymes of the pentose phosphate cycle based on activity in the whole liver. Re-feeding with a high-carbohydrate diet restored all the enzyme activities to the range of the control values with the exception of that of glucose 6-phosphate dehydrogenase, which showed the well-known ;overshoot' effect. Re-feeding with a high-fat diet also restored the activities of all the enzymes of the pentose phosphate cycle and of hexokinase; glucokinase activity alone remained unchanged. Expressed as units/g. of liver or units/mg. of protein hexokinase, glucose 6-phosphate dehydrogenase, transketolase and pentose phosphate isomerase activities were unchanged by starvation; both 6-phosphogluconate dehydrogenase and ribulose 5-phosphate epimerase activities decreased faster than the liver weight or protein content. 2. Alloxan-diabetes resulted in a decrease of approx. 30-40% in the activities of 6-phosphogluconate dehydrogenase, ribose 5-phosphate isomerase, ribulose 5-phosphate epimerase and transketolase; in contrast with this glucose 6-phosphate dehydrogenase, transaldolase and phosphoglucose isomerase activities were unchanged. Treatment of alloxan-diabetic rats with protamine-zinc-insulin for 3 days caused a very marked increase to above normal levels of activity in all the enzymes of the pentose phosphate pathway except ribulose 5-phosphate epimerase, which was restored to the control value. Hexokinase activity was also raised by this treatment. After 7 days treatment of alloxan-diabetic rats with protamine-zinc-insulin the enzyme activities returned towards the control values. 3. In adrenalectomized rats the two most important changes were the rise in hexokinase activity and the fall in transketolase activity; in addition, ribulose 5-phosphate epimerase activity was also decreased. These effects were reversed by cortisone treatment. In addition, in cortisone-treated adrenalectomized rats glucokinase activity was significantly lower than the control value. 4. In thyroidectomized rats both ribose 5-phosphate isomerase and transketolase activities were decreased; in contrast with this transaldolase activity did not change significantly. Hypophysectomy caused a 50% fall in transketolase activity that was partially reversed by treatment with thyroxine and almost fully reversed by treatment with growth hormone for 8 days. 5. The results are discussed in relation to the hormonal control of the non-oxidative reactions of the pentose phosphate cycle, the marked changes in transketolase activity being particularly outstanding.
D000315:Adrenalectomy; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology; D004032:Diet; D004702:Endocrine Glands / Q000502:physiology*; D005941:Glucokinase / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D005956:Glucose-6-Phosphate Isomerase / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D006593:Hexokinase / Q000378:metabolism; D006728:Hormones / Q000494:pharmacology; D007016:Hypophysectomy; D007535:Isomerases / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D010429:Pentoses / Q000378:metabolism*; D010734:Phosphogluconate Dehydrogenase / Q000378:metabolism; D051381:Rats; D013217:Starvation; D013965:Thyroidectomy; D014166:Transferases / Q000378:metabolism
D006728:Hormones; D010429:Pentoses; D010734:Phosphogluconate Dehydrogenase; D005954:Glucosephosphate Dehydrogenase; D014166:Transferases; D006593:Hexokinase; D005941:Glucokinase; D007535:Isomerases; D005956:Glucose-6-Phosphate Isomerase; D005947:Glucose