BIOC 3560 Lecture Notes - Lecture 7: Gsk-3, Glycogen Phosphorylase, Phosphorylase Kinase

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Phosphoryl groups added to enzymes introduce: a relatively bulky group (can result in steric exclusion, charge allowing electrostatic interactions (attraction, repulsion, oxygen atoms that can participate in hydrogen bonds, site for protein-protein interactions. Glycogen phosphorylase catalyses the phosphorolysis (breakdown using phosphate) of glycogen (glucose storage) Glycogen phosphorylase has two distinct cellular forms: phosphorylase a (active, phosphorylase b (inactive) Phosphorylase b is changed into its activated (cid:862)a(cid:863) form by phosphorylation by phosphorylase kinase. Phosphorylation is targeted to one specific residue, ser14. This stabilizes a structural state in glycogen phosphorylase. Phosphorylation of ser14 (circles) favours the r state enzyme is activated. Phosphorylation: can occur on multiple (specific) sites of a protein, can produce different degrees of effect on the function of the protein. Pka phosphorylates glycogen synthase at some sites. Glycogen synthase kinase 3 (gsk3) phosphorylates gs but at different sites. The effect of gsk3 is a more potent inhibition of glycogen synthase.

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