Glycogenolysis
GLYCOGEN
• Body's glucose reserve
• Can be mobilized more quickly/efficiently than fats
• Stored in liver & muscle
• Mobilized during fast (low insulin: glucagon)
ENZYMES OF GLYCOGENOLYSIS
Glycogen phosphorylase
• Breaks alpha (1,4) bonds
Debranching enzyme
• Breaks alpha (1,6) bonds
• Aka alpha 1,6 glucosidase
Glucose 6-phosphatase
• Tissue specific: liver only
GLYCOGENOLYSIS
1. Glycogen phosphorylase removes terminal residues of glycogen branches
• Cleaves alpha (1,4) glycosidic bonds until 4 glucose residues remain per branch
• Cleaves 1 glucose residue at a time
• Glycogen + Pi --> Glucose 1-phosphate
2. Debranching enzymes transfers 3 residues of shortest branches to longer ones
• One glucose residue remains per branch
• Creates more alpha (1,4) linkages for glycogen phosphorylase to hydrolyze
3. Debranching enzyme cleaves last glucose residue from short branches
• Cleaves alpha (1,6) bond
• Glycogen + H2O --> Glucose
• Releases residue as glucose NOT glucose 1P
4. Repeat: glycogen phosphorylase & debranching enzyme degrade glycogen to glucose & glucose 1P
LIVER VERSUS MUSCLE: FATES OF GLUCOSE & GLUCOSE 1P
• Both organs: glucose 1P reversibly converts to glucose 6P
Muscle
• Glucose 6P enters glycolysis --> Pyruvate + ATP
• If O2 is present: pyruvate decarboxylation --> acetyl CoA --> aerobic respiration
• If O2 is absent (exercising muscle): anaerobic glycolysis --> lactate
• Both pyruvate fates produce ATP: fuel for muscle cells
• Stores glycogen for its own use
Liver
• Glucose 6-phosphatase: Glucose 6P --> Glucose + Pi (enzyme NOT in muscle)
• Hepatic glucose released into circulation: fuels peripheral tissues (brain & rbc's)
CLINICAL CORRELATION
Von Gierke's Disease (Type I glycogen storage disease)
• Glucose 6-phosphatase deficiency in liver/kidney
• Frequent hypoglycemia: cannot mobilize glycogen during fast
• Treatment: frequent feedings with slowly digested carbohydrates (i.e. uncooked starch) to maintain blood glucose