Glycogen Metabolism

Types of glycogen metabolism

1. Intracellular

2. Digestive

Digestive breakdown

• unregulated

Intracellular breakdown

• Highly regulated

• stored in granules with glycoprotein (glycogenin)

• Glycogen phosphorylase breaks down glycogen to glucose when needed (phosphorolysis)

• Cleaves from non-reducing ends (exoglycosidase) → glucose-1P →glucose-6P

• can go to any pathway from there

Glucose from diet

• a-Amylase in gut breaks down glycogen/starch unregulated

• endoglycosidase (removes anywhere along glycogen chain) chain by chain →maltose and other small oligosaccharides

• Cant break down at branch points (a1-6)

• Needs debranching enzyme when chain is short enough: removes glucoses and transfers into main chain but leaves single glucose that is removed as just glucose

Glycogen Phosphorylase

• Glycosidic linkage attacks phosphate on PLP

• Excludes water from rxn

• Schiff base + carbonium ion catalyst

Glucose-6Phosphatase

• Can switch back and forth from glucose-1P to glucose-6

• Uses serine to phosphorylate glucose that can cross blood barrier

Debranching enzymes

• Transferase: transfers 3 glucoses next to branch, to next chain

• a-1-6-glucosidase : breaks off left over glucose

Branching enzyme

adds branches to glycogen (a1-6)

Regulation of Glycogen metabolism

• glycogen synthase → adds glucose to glycogen chain

• AMP activates Glycogen phosphorylase

• ATP inhibits Glycogen phosphorylase

• Glucose-6P inhibits Glycogen phosphorylase

• caffeine inhibits Glycogen phosphorylase

• Glycogen synthase activated by glucose-6P

Regulation of Glycogen phosphorylase in liver

• Active form(a) → loose

• Inactive form(b) →tight

• Binding of glucose to (a) form → inactivates it

Regulation of Glycogen phosphorylase in muscle

• activated by AMP (muscle contraction)

• ATP inhibits

• Inhibited by glucose

Regulation of Glycogen phosphorylase in both liver and muscle

• phosphorylation of serine reside activates

• Low blood glucose→ glucagon released→ phosphorylation

• Fear→ epinephrine →phosphorylation

• Phosphorylase kinase enzyme is needed and activated by Ca²⁺

Protein Kinase A

• regulated through phosphorylase kinase + Ca

• Phosphorylates glycogen phosphorylase

Enzyme Cascades

• Glucagon / epinephrine activates Adenylyl cyclase →cAMP

• activation of kinases and phosphatases that control glycogen phosphorylase

• inhibits glycogen synthase

glycogen synthesis

• Leloir: found that glycogen synthesis depends on nucleotides

• UDP-glucose pyrophosphorylase →

Glycogen Synthase

• Forms (a1-4) bonds

• starts at glycogenin protein

• First glucose linked to OH of tyrosine

• transfers glucose units from UDP-glucose to C-4 hydroxyl non reducing end of glycogen strand

Glycogen storage diseases

• Andersens Disease : defective branching enzymes → liver cirrhosis→ death

• Pompe : Glucosidase → large lysosomes → cardiorespiratory failure

• Von Gierke : Glusoce-6 phosphatase → liver enlargement

• McArdle : Phosphorylase → painful muscle cramps