What effect might a deficiency of glycogen synthase induce?
Mutations in the GYS1 or GYS2 gene lead to a lack of functional glycogen synthase, which prevents the production of glycogen from glucose. Mutations that cause GSD 0 result in a complete absence of glycogen in either liver or muscle cells.
How is glycogen synthase inhibited?
Background: Glycogen synthase kinase-3 (GSK-3) is a serine/threonine protein kinase, the activity of which is inhibited by a variety of extracellular stimuli including insulin, growth factors, cell specification factors and cell adhesion.
Why is glycogen synthase inhibited by ATP?
Glycogen synthase, is activated by G6P. When there is high demand for ATP (low [ATP], low [G6P], and high [AMP]), glycogen phosphorylase is stimulated and glycogen synthase is inhibited, so flux through this pathway favours glycogen breakdown.
What is the role of glycogen synthase?
Glycogen synthase, as discussed earlier, catalyzes the rate-limiting step in glycogen synthesis in the liver and in skeletal muscle, namely, the transfer of glucose monomers from UDP-glucose to the terminal branch of the growing glycogen chain via the formation of α(1→4) glycosidic bonds.
What decreases glycogen synthase activity?
As glucagon concentration decreases, activity of the hepatocyte adenylate cyclase decreases and cytosolic cAMP concentration falls owing to degradation by phosphodiesterase. The result is a decreased phosphorylation of glycogen synthase and phosphorylase, activation of the synthase, and inhibition of the phosphorylase.
How is glycogen synthase activated?
Glycogen synthase (GS), a key enzyme in glycogen synthesis, is activated by the allosteric stimulator glucose-6-phosphate (G6P) and by dephosphorylation through inactivation of GS kinase-3 with insulin.
What regulates glycogen synthase?
Glycogen synthase activity is regulated by phosphorylation and allosterically activated by glucose 6-phosphate. Phosphorylation of nine serines by different kinases regulates glycogen synthase affinity for glucose 6-phosphate and its substrate UDP-glucose.
How common is liver glycogen synthase deficiency in children?
Conclusion: Liver glycogen synthase deficiency is likely to be more common than is believed today. It should be sought in children who, before the first meal of the day, present with drowsiness, lack of attention, pallor, uncoordinated eye movements, disorientation or convulsions and who have hypoglycaemia and acetone in urine.
Where is the glycogen synthase isozyme gene located in the human liver?
Nuttall F.Q., Gannon M.C., Kubic V.L., Hoyt K.J. The human liver Glycogen synthase isozyme gene is located on the short arm of chromosome 12. Genomics. 1994;19(2):404–405. [PubMed] [Google Scholar] 37.
What are the consequences of glycogen synthase deficiency?
Another consequence of glycogen synthase deficiency is excess of substrates of the glycolytic pathway due to a reduced flow into glycogenosis (see Figure 1). The net effect results in transient post- prandial hyperglycemia and hyperlactatemia (5,8). However, some affected individuals may be asymptomatic or go undiagnosed (6,9).
How does glycogen break down in the liver?
Liver glycogen breaks down to maintain blood glucose concentrations on demand. Alternatively, post prandial excess blood glucose triggers insulin release, and glycogen synthesis and storage in the liver and muscles. During stress or short periods of fasting, glucagon signals the liver to break down glycogen stores into glucose (glycogenolysis).