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

Glycogenolysis

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