Glycogen metabolism in muscle and liver Flashcards
Glycogen
Polysaccharide storage form of glucose
Stored in granules predominantly in muscle and liver
Liver glycogen maintains plasma glucose
Muscle glucose sustains muscle contraction
Structure of glycogen
Found in granules within cells
Highly branched polysaccharide of glucose
(a-1,4)linked glucose molecules with an (a-1,6)branch every 8-14 glucose residues
Lots of ends for phosphorylase and glycogen synthase to act on
D glucose
Natural form used by animal cells
Glycogen brakdown
Glycogen-> gluc-1-phosphate-> gluc-6- phosphate
Second reaction catalysed by phosphoglucomutase
Glycogen breakdown in muslce
Glycogen-> gluc 1 phosphate-> gluc 6 phosphate -> pyruvate -> lactate and CO2
Glycogen breakdown in liver
Glycogen-> gluc 1 phosphate-> gluc 6 phosphate -> glucose
Liver can do this because it expresses glucose 6 phosphatase which muscle does not
Mechanism of glucose breakdown
The a-1,4 linkages broken by phosphorolysis catalysed by glycogen phosphorylase
It removes single units from non-reducing ends of glycogen to form glucose-1-phosphate
Phosphorylase
Breaks a-1,4 links up to 4 glucose units from branch point
Transferase
Activity of debranching enzyme
Removes 3 residues from branch and transfers them to end of another chain in a-1,4 linkage
a-1,6 glucosidase
Removes single glucose unit left at branch
Activity of debranching enzyme
Cleavage of a-1,6 linkages at branch points
a-1,6 linkages broken by a different a-1,6 glucosidase
Cleaves bond to form free glucose by hydrolysis
Glycogen synthesis from UDP glucose
Glucose (ADP) (Hexokinase) –>
Glucose 6 phosphate (phosphoglucomutase) –>
Glucose 1 phosphate (UTP) –>
UDP glucose (glycogen synthase) –>
Glycogen (n) - glycogen (n+1)
How glycogen synthesis starts
Priming function carried out by glycogenin protein
UDP glucose donates first glucosyl residue and attaches to tyrosine in glycogenin
Remaining glucose units added in a-1,4 linkage from UDP glucose
Introduction of branches
Glycogen synthase extends chain in a-1,4 linkage but can’t made branches
Branching enzyme transfers block of 7 residues from growing chain to create new branch with a-1,6 linkage
New branch must not be within 4 residues of existing branch
Glycogen as energy store
Enzymes phosphorylase and glycogen synthase very sensitive to regulation by hormones, stress, muscle contraction
Branched structure means large number of ends
Bad store because hydrophilic and associates with water
Acceleration of glycogen mobilisation
In liver during starvation, when glucose is required for glycolysis by the brain and red blood cells
In muscle to fuel glycolysis during vigorous exercise
Activation of glycogen synthesis
To replenish liver glycogen stores after feeding or muscle stores when exercise ceases
Pathway for glycogen synthesis not simple reversal of breakdown and requires energy input
AMP regulation of phosphorylase
Present when ATP is depleted during muscle contraction
Activates phosphorylase
ATP and glucose 6 phosphate regulation of phosphorylase
Both compete with AMP binding
Inhibit phosphorylase
Sings of high energy levels
Glycogen breakdown inhibited when these are high
Glucose 6 phosphate and glycogen synthase
Allosterically activates glycogen synthase
Glycogen synthesis is activated
Regulation of glycogen metabolism by covalent modification
Mediated by addition of phosphate group
Addition of phosphate group is known as phorphorylation and catalysed by protein kinase
Reversible modification; removal of phosphate catalysed by protein phosphatases
cAMP dependent phosphorylation of phosphorylase
cAMP cascade results in phosphorylation of serine hydroxyl of muscle glycogen phosphorylase
Promotes transition to active site
Phosphorylated enzyme less sensitive to allosteric inhibitors
If cellular ATP and glucose 6 phosphate high, phosphorylase will be activated
a
Active enzyme
Independent of allosteric regulators
e.g. phosphorylated form of glycogen phosphorylase
b
Enzyme dependent on local allosteric controls
e.g. dephosphorylated form of glycogen phosphorylase
Catabolic reactions and enzymes
The phosphorylated form of the enzyme is the active form
Anabolic reactions and enzymes
The phosphorylated form is the inactive form
