Glycogen synthase Hymenolepis diminuta. I. Allosteric activation and inhibition.
Glycogen synthase (UDP glucose: glycogen alpha-4-glycosyltransferase, EC2.4.1.11) of the tapeworm Hymenolepis diminuta exists in 2 forms: 1) the I-form (independent), which has significant activity in the absence of glucose 6-phosphate (G6P); and 2) the phosphorylated D-form (dependent), which has no enzymatic activity unless G6P is present. The activity of the I-form is greatly enhanced by a variety of allosteric effectors which have, as their common feature, 1 or more phosphate groups. These include inorganic phosphate (Pi), several sugar phosphates, some phosphorylated glycolytic intermediates, and nucleoside mono- and triphosphates. Competition studies suggest that while most of the positive effectors act at the same site on the enzyme (the "G6P site"), fructose 1,6-diphosphate (FDP) and 2,3-diphosphoglyceric acid (2,3DPG) act at low concentrations to stimulate the enzyme at another locus (the "diphosphate site"), while at high concentrations they competitively inhibit the binding of G6P and of the other activators. The inhibition by high uridine monophosphate (UMP) concentrations is competitive only with the activator uridine triphosphate (UTP), suggesting the existence of a third type of allosteric site (the "uridine nucleotide site"). This third site may be the locus for feedback inhibition by the product uridine diphosphate (UDP), a control mechanism which has been observed to occur in mammalian systems. The allosteric control of the D-form of the enzyme is comparatively simple, apparently involving only one site (the "G6P site") that binds a few effects with greatly reduced affinity. Pi reverses the activation of the D-form by G6P.
D000494:Allosteric Regulation; D000495:Allosteric Site; D000818:Animals; D004163:Diphosphoglyceric Acids / Q000378:metabolism; D005635:Fructosediphosphates / Q000378:metabolism; D005958:Glucosephosphates / Q000378:metabolism; D006006:Glycogen Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006926:Hymenolepis / Q000201:enzymology*; D014532:Uridine Diphosphate Glucose / Q000378:metabolism; D014542:Uridine Monophosphate / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology
D004163:Diphosphoglyceric Acids; D005635:Fructosediphosphates; D005958:Glucosephosphates; D014542:Uridine Monophosphate; D006006:Glycogen Synthase; D014544:Uridine Triphosphate; D014532:Uridine Diphosphate Glucose