Fig. 8: Physiological relevance of dynamic regulation of GYG1 and GYG2 and their interactions with GS in glycogen metabolism.

GYG1 and GYG2 play distinct roles in glycogen metabolism. GYG1 functions as a glycogen primer through its autoglycosylation activity, promoting glycogen synthesis and the formation of glycogen β particles. GYG2, however, lacks autoglycosylation capability and cannot compensate for GYG1’s role. Instead, GYG2 binds to glycogen synthase (GS) and enhances its phosphorylation, leading to decreased GS activity and reduced glycogen synthesis. Notably, in addition to regulating glycogen synthesis, GYG2 expression also controls glycogen particle size, as the formation of glycogen α particles requires both GYG1 and GYG2. Thus, the dynamic expression of GYG1 and GYG2 under metabolic change is crucial for maintaining glycogen balance. In the absence of GYG1 or GYG2, the regulatory mechanisms for glycogen balance are disrupted, leading to metabolic reprogramming and altered glycogen content, which affects normal physiological function. This model highlights GYG2 as a negative regulator of glycogenesis by modulating GS activity and influencing glycogen particle morphology. Created with BioRender.com.