Uric acid inhibits liver phosphorylase a activity under simulated in vivo conditions.
We have reported that glycogen synthesis and degradation can occur in vivo without a significant change in the amount of phosphorylase a present. These data suggest the presence of a regulatable mechanism for inhibiting phosphorylase a activity in vivo. Several effectors have been described. AMP stimulates, whereas ADP, ATP, and glucose inhibit activity. Of these effectors, only the glucose concentration changes under normal conditions; thus it could regulate phosphorylase a activity in vivo. We previously have reported that, when all of these effectors were present at physiological concentrations, the net effect was no change in phosphorylase a activity. Addition of caffeine, an independent inhibitor of activity, to the above effectors not only resulted in inhibition but also restored a glucose concentration-dependent inhibition. Because uric acid is an endogenous xanthine derivative, we decided to determine whether it had an effect on phosphorylase a activity. Independently, uric acid did not affect activity; however, when added at a presumed physiological concentration in combination with AMP, ADP, ATP, and glucose, it inhibited activity. A modest but not statistically significant glucose concentration-dependent inhibition was also present. Thus uric acid may play an important role in regulating phosphorylase a activity in vivo.
Ercan-Fang
N G
NG
Metabolic Research Laboratory and Section of Endocrinology, Metabolism and Nutrition, Minneapolis Veterans Affairs Medical Center, One Veterans Drive (111G), Minneapolis, MN 55417, USA. ercan001@tc.umn.edu
Nuttall
F Q
FQ
Gannon
M C
MC
D000227:Adenine Nucleotides / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D008099:Liver / Q000201:enzymology*; D008297:Male; D009994:Osmolar Concentration; D010762:Phosphorylase a / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014527:Uric Acid / Q000494:pharmacology*
D000227:Adenine Nucleotides; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D014527:Uric Acid; D002110:Caffeine; D010762:Phosphorylase a; D005947:Glucose