Highlights of Glycogen Metabolism II
In the notes below, I refer to Glycogen Phosphorylase a as GPa and Glycogen Phosphorylase b as GPb. I also refer to Glycogen Synthase a as GSa and Glycogen Synthase b as GSb. You are welcome to do the same.
1. Glycogen phosphorylase is present in two covalently different forms, GPa and GPb. They differ in phosphorylation. GPa is phosphorylated and GPb is not.1. GPb is converted into GPa by phosphorylation at two sites. Covalent modifications are DIFFERENT from allosteric controls, which interconvert the R and T states of BOTH GPa and GPb.
2. The different glycogen phosphorylase forms have different allosteric regulation, as well. GPb is converted to the R state by AMP and converted to the T state by ATP and G6P. The latter two are more commonly abundant in the cell than AMP, so we think of GPb as less active. GPa is converted to the T state by glucose (rarely present much). When glucose is absent, GPa is automatically in the R state. Thus, we think of GPa as the more active form.
3. Phosphorylation of GPb to make GPa is catalyzed by an enzyme known as phosphorylase kinase. Full activation of phosphorylase kinase requires both calcium ions and phosphorylation by protein kinase A
4. Thus, the binding of epinephrine to the cell surface stimulates the following events in muscle relating to glycogen breakdown
5. Glycogen synthase (catalyzes formation of glycogen) exists in two different covalent forms - GSa (has no phosphate and is the most active) and GSb (has phosphate and is the least active).
6. Thus, binding of epinephrine or glucagon to a cell surface receptor ultimately results in the phosphorylation of GPb and GSa to make GPa and GSb, respectively. The products of these phosphorylations - GPa and GSb have opposite activities. GPa is MORE ACTIVE and GSb is LESS ACTIVE. Thus, reciprocal regulation of glycogen metabolism is mediated through phosphorylation and dephosphorylation. The conversion of R and T states occurs allosterically.
7. Reversal of the process (removal of the phosphates of all of the phosphorylated enzymes) occurs as the result of catalysis by phosphoprotein phosphatase (PP-1). PP-1 is stimulated to be active by insulin. Thus, increasing glucose concentration in the bloodstream causes insulin to be released, which causes cells to take up glucose and also (inside the cell) to cause the glucose to be made into glycogen. I'll talk more next time about how PP-1 is regulated.