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S 2007 BIOC 3406

S 2007 BIOC 3406. 02-06-07. Glycogen. Rapid access glucose Made in (almost) all cells Primarily made in liver, muscles Liver glycogen to replenish blood glucose Muscle glycogen to use as fuel, building material. Glycogen. Storage in liver (~10% maximum) lasts ~24 h

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S 2007 BIOC 3406

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  1. S 2007 BIOC 3406 02-06-07

  2. Glycogen • Rapid access glucose • Made in (almost) all cells • Primarily made in liver, muscles • Liver glycogen to replenish blood glucose • Muscle glycogen to use as fuel, building material

  3. Glycogen • Storage in liver (~10% maximum) lasts ~24 h • Storage in muscle (~2% maximum) much smaller lifetime

  4. Glycogen • Why stored as glycogen? • Reduces osmotic burden of cell • As glucose would be ~0.4M! • Particles about the thickness of the cell membrane • up to 55,000 glucoses per particle • up to 2000 nonreducing ends (branched structure)

  5. Nonreducing end

  6. Glycogen breakdown

  7. Glycogen phosphorylase • Uses Pi • Pyridoxal phosphate cofactor PLP used in transamination • Chops off a glucose 1-phosphate from nonreducing end • Stops four glucoses from an (1-6) branch point • Resumes work after branch removed

  8. Debranching enzyme • Transfers a branch to nonreducing end, leaving one glucose branch (tranferase activity) • Removes single glucose (NOT G 1-P)

  9. Liver glucose 6-phosphate • Converted to glucose for blood sugar augmentation • Must enter endoplasmic reticulum (transporters) • glucose 6-phosphatase on inside wall • Leaves cell (another transporter)

  10. Glycogen synthesis

  11. Glucose, glucose 6-phosphate, glucose 1-phosphate • G must be phosphorylated (hexokinase) to G 6-P, then isomerized (phosphoglucomutase) to G 1-P • G 6-P must be isomerize • G 1-P is ready to go Glucose 1-phosphate + UTP  UDP-glucose + PPi

  12. In our case G 1-P In our case UTP

  13. UDP Glucose • A sugar nucleotide • Able to release PPi, exothermic • A “handle” with surface intermolecular interaction potential • Nucleoside monophosphate is a good leaving group • Inventory manager

  14. Glycogen synthase • Adds glucose (via UDP-glucose) to nonreducing end of growing glycogen chain • Releases UDP • Chain must be longer than 4 units

  15. Glycogen-branching enzyme • At least two other names • Amylo (14) to (16) transglycosylase • Glycosyl-(46)-transferase • Moves a 6 or 7 glucose chain to a more interior position on a chain • Unbranched end must be at least 11 long

  16. Glycogenin • Glycogen particle “grows” on glycogenin • Glycogenin catalyzes the addition of 8 glucoses via UDP glucose to start particle • Glycogen synthase, glycogen branching enzyme take over after the formation of the 8-glucose chain

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