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Glycogen Metabolism

Glycogen Metabolism. Before we get to glycogen: Dietary sugars. Glycogen. Branched every 8-12 residues Up to 50,000 or so residues total. Amylopectin : branch every 25 residues. Glycogen Synthesis and Breakdown . Glycogen synthesis and breakdown are both controlled by hormones

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Glycogen Metabolism

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  1. Glycogen Metabolism

  2. Before we get to glycogen: Dietary sugars

  3. Glycogen • Branched every 8-12 residues • Up to 50,000 or so residues total Amylopectin: branch every 25 residues

  4. Glycogen Synthesis and Breakdown • Glycogen synthesis and breakdown are both controlled by hormones • Glucagon, Epinephrine • turn on glycogen breakdown • Turn off glycogen synthesis • Hormones act through receptors on cell surface and G-proteins Glucagon Epinephrine

  5. Regulation of Glycogen Metabolism fasting Fed state Via cAMP Via PIP3 Insulin: secreted by pancreas when Glc high inc rate of transport into cell and glycogen syn Glucagon: secreted when Glc low Epi: released by adrenal gland in response to neural signal (flight or flight)

  6. Intracellular Regulation of Glycogen Low [Glc] Simultaneous effect

  7. Intracellular Regulation of Glycogen High [Glc]

  8. Breakdown: Glycogen Phosphorylase

  9. Breakdown: • Glycogen phosphorylase cleaves glycogen at non-reducing end to generate glucose-1-phosphate • Debranching of limit dextrInoccurs in two steps. • 1st, 3 X 1,4 linked glucose residues are transferred to non-reducing end of glycogen • 2nd, amylo-1,6-glucosidase cleaves 1,6 linked glucose residue. • Glucose-1-phosphate is converted to glucose-6-phosphate by phosphoglucomutase

  10. How Is Glycogen Synthesized ? • Metabolism of Glucose 1-Phosphate • Phosphoglucomutasecatalyzes the conversion of glucose 1-phosphate to glucose 6-phosphate

  11. Glycogen Synthesis • Glycogen Synthase adds glucose residues to glycogen • Synthasecannot start from scratch – needs a primer • Glycogenin starts a new glycogen chain, bound to itself De novo synthesis of glycogen is built on a protein, glycogenin, (a tyrosine glucosyltransferase). The first glucose is linked to a tyrosine -OH on the protein.

  12. How Is Glycogen Synthesized ? The mechanism of the UDP-glucose pyrophosphorylasereaction. Attack at the α-phosphorus of UTP by a phosphate oxygen of glucose-1-P is followed by departure of the pyrophosphate anion. Subsequent hydrolysis of the PPi pulls the reaction to completion.

  13. Glycogen synthase catalyzes the major regulatory step • Synthesis of glycogen from glucose 6-phosphate

  14. Glycogen Synthase Reaction Glycogen synthase catalyzes loss of UDP with formation of a carbocation which is attacked by a 4’ OH on a nonreducing end of glycogen. The enzyme requires a short primer, (4-8 residues).

  15. Glycogen Branching Reaction Glycogen branching enzyme forms the α (1-6) branch points. (This enzyme is distinct from the catabolic debranching enzyme.) Six- or seven-residue segments of a growing glycogen chain are transferred to the C-6 hydroxyl group of a glucose residue on the same or a nearby chain. This leaves 4 residues at the branch point to act as substrate for glycogen synthase.

  16. Glycogen storage diseases • are genetic enzyme deficiencies that result in excessive glycogen accumulation within cells. Additional symptoms depend on the particular enzyme that is deficient.

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