Post on 16-Sep-2020
Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005
Glycogen metabolism
Biochemistry
2017Hayder A Giha
Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005
Glycogen metabolism
l Glycogen found mainly in Liver (blood) and muscle (local)
l Synthesis of glycogen, (glycogenesis)
l Degradation of glycogen (glycogenolysis)
Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005
Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005
Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005
Glycogen synthesisl Liver glycogen is for storage and maintenance of
blood glucose between mealsl After 12-18 hours of fasting the liver completely
depleted of glycogenl Muscle glycogen for local use, depleted only after
vigorous exercise. It is not affected short-term fasting (few days), and only moderately affected by prolonged starvation (few weeks)
l Glycogen storage diseases are inherited disorders, either abnormal glycogen or deficient mobilization cause muscle weakness or even death
Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005
Glycogen synthesisl The substrate is UDP-glucosel Enzyme glycogen synthase (a1-4)l Branching enzyme (a1-6)l Initiation need either: a. a. Pre-existing short chains of glycogen or b. b. Glycogenin (protein found in center of
glycogen granule) l Progress at non-reducing end (c4 or c6)
Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005
UDP-glucose
• Glucose 6-P Glucose 1-P
• Glucose1-P + UTP UDP-Glucose + PPi
Phosphoglucomutase
UDP-glucose pyrophosphorylase
C1 of activated Glu form a glycosidic bond with C4 of terminal Glu residue of glycogen primer or OH of tyrosine of glycogenin primer. In the later, glycogen initiator synthase enzyme is used.
Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005
Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005
Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005
Branchingl When chain length 10 – 12 glucosyle residuesl Branching enzyme remove 5 – 8 residues to
another glucose in original chain l Link it through a1-6 (branch)l The branch grow by a1-4 linkagel The free C4 and C6 are reactive sites (non-
reducing site or terminal) l The increasing number of branches enhance both
synthesis and degradation
Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005
Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005
Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005
Glycogenolysis (degradation) l Removal of glucose from glycogenl It is not the reverse of glycogenesisl Enzymes are:* glycogen phosphorylase* debranching enzyme
l Site: non-reducing end (C4/C6)l i P is used to break a1 -4 linkl Product: * glucose 1-P * glycogen – smaller by one glycosyle residue
Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005
Debranching l When branch became only 4 residues (limited
dextrin)l Debranching enzyme remove 3 residues to another
branchl The elongated chain can be shortened by
phosphorylase until ONE residue linked by a1-6 is left
l The a1-6 residue is removed by debranching enzymel All G-1P converted to G-6P, in liver (kidney) G-6P
can be converted to Glu by glucose-6-phosphatase
Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005
Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005
Regulation l Different between liver and muscles due to diff.
goalsl Breakdown and synthesis are opposing, so that
they are reciprocally regulated i.e. when one activated other inhibited. To avoid futile cycles (waste of energy in form of heat)
l In muscles: a. When four Ca++ bind calmodulin, the later
undergoes conformational changes, that leads to activation of phosphorylase (glycogenolysis) by phosphorylase kinase
b. High level of AMP increase glycogenolysisl In liver:
- Glucose inhibit phosphorylase
Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005
Regulation l Phosphorylase a [P] – active form:
- Activated by phosphorylase kinase- Inhibited by protein phosphatase-1
l Glycogen synthase a [de-P] – active forml - activated by protein phosphatase-1 l - inhibited by phosphorylase kinase
Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005
Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005
Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005
Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005
Harvey RA, Champe PC. Lippincott Illustrated Biochemistry 3rd Edition, 2005