Glycogenesis and Glycogenolysis Flashcards
Glycogen breakdown in muscle
Will only breakdown to make ATP, for its own benefit
Glycogen breakdown in liver
Via glut2, the glucose will be sent to other tissues through the blood
Amount of glycogen in muscle and liver
400 g muscle
100 g liver
Insulin independent tissues
Must tissues (adipose, muscle...) Use glut4
Insulin dependent tissues
Erythro/leukocytes, lens, cornea, liver (uses glut2), brain
Insulin stimulated translocation of glut4 to membrane
- Insulin binds to tyrosine kinase (PKB)
- Activated receptor promotes glucose transporters to membrane
- Glucose transporters allow glucose uptake into cell
Amp stimulated protein kinase translocation of glut4
In low insulin levels, muscles need glucose for energy. So high AMP and low ATP (from adenylate kinase reaction) will stimulate AMPK which will promote the translocation of glut4 transporters to the membrane during muscle contraction.
Hexokinase
Km=.2mM
Constitutive enzyme (always have optimum levels)
In all tissues
Inhibited by product
Glucokinase
Km=10mM
Induced enzyme (only optimum levels with inducer insulin)
In liver
Not inhibited by product
Increase glucose = increase activity
Where is GK when you’re fasting?
Bound to GKRP (in hepatocyte nucleus)
How does GK release from GKRP to cytosol?
High glucose and high F1P
Low F6P
Glycogenesis overview
- Glucose to G6P using hexokinase or GK (ATP hydrolysis)
- G6P to G1P
- G1P and UTP react making UDPGlucose and PPi
- UDPGlucose is added to NR end of glycogen primer via glycogen synthase, liberated UDP
- UDP and ATP will regenerate UTP
Without a pre existing glycogen fragment, how is glycogen made?
Glycogenin will serve as a receptor of glucose residues. It is a protein dimer with RTKs are arranged head to toe.
Glycogen synthetase
Forms alpha 1-4 bonds
Branching enzyme
Glucosyl-4:6 transferase attaches alpha 1-6 bonds
Glycogenolysis overview
Glycogen phosphorylase will phosphorylate a glucose at the NR end and will cause glycogen breakdown
Glycogen phosphorylase specificity
Will cleave glycogen up to glucose molecule away from a branch, so a debranching enzyme will do the rest: a transferase will transfer the last 3 of the branch to the existing glycogen chain, and an alpha16 glucosidase will cleave off the branched glucose
Regular levels of blood glucose
70 - 100 mg/dL
When glycogen phosphorylase and glycogen synthase are phosphorylated, what happens?
Phosphorylated glycogen phosphorylase = active = glycogen breakdown
Phosphorylated glycogen synthase = inactive = no glycogen synthesis
Active protein kinase a =
Phosphorylated phosphorylase kinase which will phosphorylate glycogen phosphorylase (= glycogenolysis), glycogen synthase (= no glycogenesis), and inhibitor 1 (= inhibit inhibitor (phosphoprotein phosphotase) = glycogenolysis).
Glycogen synthase kinase 3
Phosphorylates glycogen synthase making it inactive
What happens when epinephrine binds to alpha antagonist receptor?
Epi binds, activating specific G proteins to activate PLC. PLC turns PIP2 into IP3 and DAG. IP3 will then release Ca2+ from the ER. Calmodulin is then formed and PKC is also activated. Calmodulin will phosphorylate phosphorylase kinase and will phosphorylate glycogen phosphorylase and synthase. The calmodulin dependent protein kinase and PKC will also phosphorylate glycogen synthase.
Regarding glycogen metabolism, insulin will
Limit cAMP production
Activate hepatic protein phosphotases
Activate phosphodiesterase that converts cAMP to AMP
Inactivate glycogen synthase kinase 3
A high insulin/glucagon ratio means
More insulin, less glucagon, favoring glycogen synthesis
