Date of Award
Doctor of Philosophy
John T. Smith
Ada Marie Campbell, Gail W. Disney, Robert H. Feinberg
In order to investigate the effect of dietary phosphate additives on glycogenesis, rats were fed standard diets supplemented with cyclotetraphosphate, cyclotriphosphate or hexametaphosphate at a 0.1% level of phosphorus. A control group was fed orthophosphate at a similar level. After two weeks half of the animals received a test dose of 14C-glucose administered by stomach tube. After 2-1/2 hours their livers were removed to determine the incorporation of 14C-glucose into glycogen and total glycogen recovered. The remaining animals were sacrificed and their livers were removed to determine glycogen synthetase activity. Animals fed cyclotetraphosphate exhibited lower levels of glycogen synthetase activity, 14C-glucose incorporation into glycogen and total glycogen synthesized than did those rats fed orthophosphate. In contrast, animals fed cyclotriphosphate and hexametaphosphate showed a stimulatory effect on the same three parameters when compared to orthophosphate controls.
To determine the minimum length of feeding time necessary to achieve these metabolic effects experimental diets were fed to animals for increasing lengths of time (24 hours, 48 hours, 96 hours, 144 hours and 192 hours) at a 0.1% level of phosphorus. An inhibition of the independent (I) and total glycogen synthetase activity relative to that observed with feeding of orthophosphate was evident in female rats fed cyclotetraphosphate for 24, 48, 144 and 192 hours but not at 96 hours and in males at all time intervals except 24 hours. Males and females fed cyclotriphosphate and hexametaphosphate had glycogen synthetase activity ( I and total) comparable at all time intervals to that of animals fed orthophosphate suggesting that longer dietary periods may be necessary. 14C-glucose incorporated into liver glycogen and total liver glycogen in male rats was lower in animals fed cyclotetraphosphate than in rats fed orthophosphate for all time intervals except 24 hours. Female rats fed cyclotetraphosphate had essentially the same values as females which were fed orthophosphate.
To determine if there was a threshold level for the development of metabolic effects diets containing increasing percentages (0.01%, 0.02%, 0.04%, 0.06%) of phosphate supplementation were fed to animals for two weeks. In general, at all levels of supplementation male and female rats fed cyclotetraphosphate exhibited lower glycogen synthetase activity than animals fed orthophosphate. A stimulatory effect on enzyme activity in males fed cyclotriphosphate was evident at 0.04% and 0.06% and.in females at 0.02% and 0.04% phosphate supplementation. The incorporation of 14C-glucose into liver glycogen and total glycogen recovered from male rats fed cyclotriphosphate and hexametaphosphate was increased and in rats fed cyclotetraphosphate decreased at levels as low as 0.01% phosphate supplementation. Similar effects on these parameters were seen in females at 0.04% and 0.06% phosphate supplementation.
The activity of the dependent form of glycogen synthetase may be estimated by subtracting the independent activity from the total enzyme activity. The percentage of total activity made up of the dependent form of the enzyme was higher in rats fed cyclotetraphosphate than in rats fed orthophosphate. However, rats fed cyclotriphosphate and hexametaphosphate had a lower percentage of dependent activity than animals fed orthophosphate. Similar results were evident in male and female rats.
These data suggest an inhibition by cyclotetraphosphate and a stimulation by cyclotriphosphate and hexametaphosphate on the phosphorylation system controlling glycogen synthetase in the liver.
Laiming, Virginia Ann, "An Effect of Cyclotetraphosphate, Cyclotriphosphate and Hexametaphosphate on Glycogenesis in Rat Liver. " PhD diss., University of Tennessee, 1981.