The importance of nucleoside triphosphate inhibition of liver glycogen synthase phosphatase activity.
The liver glycogen particle contains constitutive glycogen-synthase phosphatase activity which is inhibited by ATP-Mg in a concentration-dependent manner within the physiological range (I0.5 = 0.1 mM). Therefore, we determined whether other nucleoside triphosphate-magnesium complexes also inhibit synthase phosphatase activity. UTP-Mg, CTP-Mg and GTP-Mg were all found to be inhibitory. The maximum inhibition was 85-90% which was greater than that for ATP-Mg. The I0.5 for UTP-Mg was comparable to that of ATP-Mg but it was greater for CTP-Mg and for GTP-Mg. At in vivo physiological concentrations, both UTP and ATP are possible inhibitors of synthase phosphatase activity. In the presence of a saturating concentration of ATP-Mg, added UTP-Mg increased the inhibition suggesting the presence of at least two distinct nucleotide binding sites. Substitution of calcium for magnesium in an ATP complex had no effect on the I0.5, but increased the maximum inhibition. The present studies also suggest that in the multistep conversion of synthase D to synthase I, ATP-Mg inhibition occurs early in the sequence. Addition of glycogen, a known inhibitor of synthase phosphatase activity, to a reaction mixture containing 3 mM ATP-Mg did not further inhibit synthase phosphatase activity when added at concentrations up to 22 mg/ml. The latter data suggest that the presence of a nucleoside triphosphate may desensitize the phosphatase to glycogen inhibition. ATP-Mg and, to a lesser extent, UTP-Mg and CTP-Mg all stimulated phosphorylase phosphatase activity but GTP-Mg did not.
Gilboe
D P
DP
Veterans Administration Medical Center, Mineapolis, MN 55417.
Nuttall
F Q
FQ
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D003570:Cytidine Triphosphate / Q000494:pharmacology; D006007:Glycogen-Synthase-D Phosphatase / Q000037:antagonists & inhibitors*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D051381:Rats; D012265:Ribonucleotides / Q000494:pharmacology*; D014532:Uridine Diphosphate Glucose / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology
D012265:Ribonucleotides; C036852:magnesium GTP; D003570:Cytidine Triphosphate; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D010749:Phosphoprotein Phosphatases; D006007:Glycogen-Synthase-D Phosphatase; D008274:Magnesium; D014544:Uridine Triphosphate; D014532:Uridine Diphosphate Glucose