生物化学原理教学（杨荣武）Chapter27 Glycogen metabolism.pptVIP

10/9/2002 Glycogen metabolism Outline Glycogen Breakdown Glycogen Synthesis Regulation of Glycogen Metabolism Glycogen Glycogen serves as storage carbohydrate in animals, insects and fungi Heavily branched to allow rapid mobilization of Glc Why use glycogen for energy storage? Muscles cannot mobilize fat as rapidly as glycogen. Fatty acid residues of fat cannot be metabolized anaerobically. Animals cannot convert fatty acids to Glc, so fat metabolism alone cannot adequately maintain essential blood Glc levels. Glycogen Breakdown Requires Three Enzymes Glycogen Phosphorylase Dimer of identical 97 kDa subunits Structural Domains and Binding Sites Each phosphorylase subunit has N- and C-terminal domains. Allosteric effector binding sites and modification sites are in the N-terminal domain. Cofactor is linked in the C-terminal domain. The catalytic site is located at the interface of glycogen binding subdomain and regulatory domain with the C-terminal domain. Pyridoxal Phosphate is an Essential Cofactor for Phosphorylase Pyridoxal-5-phosphate (PLP), a vitamin B6 derivative, is covalently linked to phosphorylase via a Schiff base to Lys 679. In an unusual role, only the phosphate group participates in the catalytic process. 3D Structure Model of Glycogen Phosphorylase Glycogen phosphorylase reaction mechanism Formation of an E?Pi?glycogen ternary complex Oxonium ion intermediate (I) formation from the ?-linked terminal glucosyl residue involving acid catalysis by Pi facilitated by proton transfer from PLP. Reaction of Pi with overall retention of configuration around C1 to form ?-D-Glc-1-phosphate. The glycogen, minus one residue, cycles back to step 1. Glycogen Debranching Enzyme Two active sites for two different catalytic activities-a bifunctional enzyme Acts as an ?(1?4) transglycosylase (glycosyl transferase) by transferring an ?(1?4) linked trisaccharide unit from a “limit branch” of glycogen to the nonreducing end of another branch. Also catalyzes the hydr