Glycogenolysis
Glycogenolysis
Glycogenolysis
INTRODUCTION
Glucose- preferred energy for the brain; required energy source for cells with few or no mitochondria Primary sources of blood glucose: - diet - not always a reliable source of glucose, sporadic - gluconeogenesis - this can provide sustained synthesis of glucose but is slow in responding to a falling blood glucose level
- degradation of glycogen - glycogen is rapidly released from the liver & kidney; when glycogen decreases, specific tissues synthesize glucose DE NOVO (AA as source of C for gluconeogenesis) - muscle glycogen - serves as fuel for ATP synthesis during muscle contraction - liver glycogen - maintains blood glucose conc. in early stages of a FAST
Glycogenolysis
Breakdown of glycogen Enzymes are different from glycogenesis Happens during the FASTING state AIM: break down glycogen to produce glucose or ATP Main enzyme: glycogen phosphorylase
Steps in Glycogenolysis
1. Shortening of chains 2. Removal of branches 3. Conversion of glucose 1-phosphate to glucose 6-phosphate
1. Shortening of chains
ENZYME: glycogen phosphorylase cleaves the (14) glycosidic bonds between the glucosyl residues at the non-reducing end Reaction: simple phosphorolysis producing glucose 1-phosphate Coenzyme: pyridoxal phosphate STOPS: when 4 glucosyl residues remain (dextrin)
Glycogen phosphorylase stops when there are only 4 remaining residues (limit dextran)
2. Removal of branches
Single bifunctional protein (debranching enzyme) has 2 components that will break down the dextrin (last 4 glucosyl residues)
Oligo (14) (14) glucan transferase
Removes the 3 remaining glucosyl residues Then attaches the residues to the nonreducing end thus elongating the chain Added residues can then be attacked by glycogen phosphorylase
Fate of G6P
Glycogenolysis Regulation
2 ways: 1. Allosteric regulation 2. Hormonal regulation
Remember:
Glycogenolysis (glycogen breakdown) enzyme is glycogen phosphorylase Glycogenesis (glycogen synthesis) enzyme is glycogen synthase
4. The Ca-Calmodulin complex activates the enzyme phosphorylase kinase 5. Phosphorylase kinase in turn activates glycogen phosphorylase 6. glycogenolysis
Hormonal Regulation
Remember that during stress or fasting state: High glucagon High epinephrine During well-fed state: High insulin
1. Glucagon or epinephrine binds to GPCR 2. subunit of G protein dissociates and binds to adenylyl cyclase (AC) 3. Activated AC converts ATP to cAMP
4 5
6
5. The C subunit activates glycogen phosphorylase kinase b by phosphorylating it 6. Glycogen phosphorylase kinase b (inactive) becomes glycogen phosphorylase kinase a (active)
Remember: active form of glycogen phosphorylase kinase is phosphorylated
8 7
7. Glycogen phosphorylase kinase a activates glycogen phosphorylase b (inactive) by phosphorylating it 8. Glycogen phosphorylase a then proceeds to glycogenolysis
Remember: active form of glycogen phosphorylase (a) is phosphorylated
1. Glucagon or Epi binds to GPCR 2. subunit of G protein dissociates and binds to AC thus activating AC 3. AC converts ATP to cAMP 4. cAMP activates PKA 5. Catalytic (C) subunit dissociates from Regulatory (R) subunit
6. C subunit inactivates glycogen synthase by phosphorylating it 7. Glycogenesis inhibited Remember: glycogen synthase b (inactive form) is inactive because it is phosphorylated.
Phosphorylated Dephosphorylated
Dephosphorylated Phosphorylated
Enzyme that phosphorylates always kinase Enzyme that Dephosphorylates always phosphatase