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Regulatory Influences

Glycogen synthesis is regulated by the activation of Protein kinase A (PKA) bound to cAMP
Glycogen degradation is regulated by the activation of phosphorylase kinase which is dictated by activated PKA

Glycogen metabolism is prone to a number of regulatory influences, all of which impact glycogen synthase (GS) and/or phosphorylase. GS is the rate-limiting enzyme in glycogen synthesis, and phosphorylase is the enzyme that catalyzes the phosphorolysis of α-1,4-glycosidic linkages. Gene PPP1R3C (PTG) is a regulatory subunit of protein phosphatase 1 (PP1), and a regulator of GS and phosphorylase. PTG is expressed in every tissue, and is most abundant in the skeletal muscle, heart, and liver. PTG binds glycogen, the primary enzymes involved glycogen metabolism regulation, GS and phosphorylase. Disruption of the PTG gene has been proven to substantially decrease glycogen stores in tissue culture cells.

PTG has also been proven to interact with laforin. The over expression of PTG was proven to accumulate glycogen in tissue culture cells and ex vivo organ models. When determining whether or not malin and laforin inhibit PTG activity, it was discovered that the cells transfected with PTG, malin, and laforin contained a similar amount of glycogen as cells transfected with a vector control. It has been concluded that malin and laforin independently decrease PTG-stimulated glycogen accumulation, but cumulatively eliminated PTG-stimulated glycogen accumulation.

PTG and gene PPPIR3D (R6) are expressed in a wide range of human tissues, whereas the other three PP1 targeting subunits, such as GL (gene PPPIR3B), display tissue specific expression patterns in skeletal muscle, heart and/or liver tissue. PTG, R6 and GL were all proven to increase glycogen accumulation. Malin and laforin were proven to inhibit R6-stimulated glycogen accumulation without inhibiting GL-stimulated glycogen accumulation. In conclusion, malin and laforin were proven to inhibit PP1 regulatory subunit-stimulated glycogen accumulation of some, but not all PP1 regulatory subunits.

Relating article: Malin decreases glycogen accumulation by promoting the degradation of protein targeting to glycogen (PTG)

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