Glycogen synthase (liver isoform) (GYS2)

Glycogen synthase is the key regulatory enzyme in the hepatic glycogen synthesis pathway, catalyzing the elongation of α-1,4-linked glucose chains from UDP-glucose onto a growing glycogen polymer[3][6][7][9]. The liver isoform (GYS2) is essential for maintaining blood glucose homeostasis, particularly during fasting. Glycogen synthesis is initiated by glycogenin, which acts as a primer; glycogen synthase extends these chains, and the branching enzyme introduces α-1,6-linkages[6][9]. GYS2 activity is tightly regulated by reversible phosphorylation and by allosteric signals—primarily glucose-6-phosphate—thus integrating hormonal (insulin/glucagon), nutritional, and cellular energy cues[1][2][3]. Aberrations in this pathway are implicated in diabetes, insulin resistance, and various glycogen storage disorders[9]. As such, the enzyme and pathway represent important therapeutic targets for metabolic disease intervention.

Other names

Glycogen synthase 2UDP-glucose:glycogen glucosyltransferaseGYS2 (liver isoform)

Allosteric activation by glucose-6-phosphate; Inhibition by phosphorylation (primarily by glycogen synthase kinase-3 and other kinases)