Glycogen metabolism in muscle and liver Flashcards
What is glycogen
Polysaccharide – storage form of glucose
Stored in granules predominantly in liver and muscle (energy reserve)
how is glycogen used
Formed from dietary glucose by glycogenesis
Liver glycogen utilised to maintain plasma glucose levels between meals, glycogen in muscle required to sustain contraction
Glycogen is degraded between meals in liver by glycogenesis pathway to produce glucose-1-phosphate (converted to free glucose, exported to blood to maintain levels or broken down in muscle as energy for contraction)
More glycogen is stored in muscle
10% weight of liver but 2% muscle but muscle 40% of human body weight and liver is 2.5%
Liver contains less glycogen that is required to sustain glucose metabolism for 24 hours so requires gluconeogenesis
Structure of glycogen
Highly branched polysaccharide of glucose consisting of (a-1,4) linked glucose molecules with a (a-1,6) branch every 8-14 glucose residues
Important to provide large number of ends which phosphorylase and glycogen synthase can act to ensure rapid breakdown and resynthesis
Which linkages used to form glycogen
a-D-glucose joined by a-1,4 and a-1,6 linkages
Glycogen breakdown (glycogenolysis)
In time of metabolic needs, cells breakdown down stored glycogen rapidly using a combo of signals
Known as mobilisation
Breakdown products meet different needs in liver and muscle
Glycogen breakdown in muscle
glycogen to G1P to G6P to pyruvate to lactate and CO2
mobilises to fuel muscle’s energy requirements via glycolysis to support contraction
Glycogen breakdown in liver
glycogen to G1P to G6P to glucose
to export to other tissues as it expresses G6Pase which muscle doesn’t
Phosphate group keeps in inside cells as cant cross membrane
Mechanism of glycogen breakdown
a-1,4 linkages are broken by phosphorolysis, catalysed by the enzyme glycogen phosphorylase
removes single units from non-reducing ends of glycogen to form G1P
Same as hydrolysis but with phosphate, not water
ATP not involved
Glycogen degradation
Phosphorylase can only break a-1,4 links up to within 4 glucose units from a branch point
Transferase activity of debranching enzyme removes 3 residues from branch and transfers to end of another chain in an a-1,4 linkage
The single glucose unit left at branch is removed by action of a-1,6 glucosidase activity of debranching enzyme
Chain can be broken down by phosphorylase until it meets next branching point
when does glycogenolysis occur
in response to low glucose in plasma or muscle contraction
Glycogen synthesis (glycogenesis)
Glycogen formed from UDP-glucose
Glucose (+ATP) - G6P - G1P (+UTP) - UDP-G (high E form of glucose) - glycogen to glucose releasing UDPConsumption of UTP is energetically equivalent to ATP consumption
Formation of glycogen from UDP-glucose
Glycogen synthase adds glucose units in a-1,4 linkage onto glycogen chain using UDP-glucose
How does glycogenesis start
Glycogen synthase can only add to pre-existing chain of more than 4 glucosyl residues
The priming function is carried out by a protein glycogenin
UDP-glucose donates first glucosyl residue and attaches it to amino acid tyrosine in glycogenin
Glycogenin extends glucose chain up to 7 additional residues from UDP-glucose via a-1,4 linkages
Introduction of branches in glycogenesis
Glycogen synthase extends chain in a-1,4 linkages but cannot make branches
Branching enzyme transfers a block of 7 residues from a growing chain to create a new branch via an a-1,6 linkage
New branches can’t be within 4 residues of pre-existing branches
Glycogen as an energy store
Good as can be mobilised rapidly
Enzymes phosphorylase and glycogen synthase are sensitive to hormones, stress, muscle contraction
The branched structure = large number of ends so can be added to or broken down
But is hydrophilic so associates with water, increasing weight and bulk
Regulation of glycogen metabolism
glycogenolysis accelerated by (liver) extended fasting and (muscle) vigorous exercise
glycogenesis activated to replenish liver stores after eating or muscles after exercise, require energy input
Allosteric regulation of phosphorylase
Glycogen phosphorylase in muscle is subject to allosteric regulation by AMP, ATP and G6P
AMP (present when ATP is depleted during muscle contraction) activates phosphorylase
ATP and G6P (both compete with AMP binding, inhibit phosphorylase, signs of high energy levels)
Glycogen breakdown inhibited when ATP and G6P plentiful
Allosteric regulation of glycogen synthase
Glycogen synthase is allosterically activated by G6P, activated when G6P plentiful and depleted when its not (activated phosphorylase)
liver allosteric control
mainly by the supply of glucose to cell (glucose and G6P), muscle controlled by energy status (ATP and AMP) and substrate availability (G6P)
Regulation of glycogen metabolism by covalent modification
Mediated by addition (and removal) of phosphate group
Addition of phosphate group is phosphorylation and is catalysed by protein kinases
Reversible modification, removal of phosphate groups is catalysed by protein phosphatases
Induction of cAMP cascade effect on glycogen synthesis
cAMP cascade results in phosphorylation of hydroxyl group in a serine residue of glycogen phosphorylase, promotes transition to active state
phosphorylated enzyme is less sensitive to allosteric inhibitors, even if cellular ATP levels and G6P are high phosphorylase will be activated
opposite effect on glycogen synthase
phosphorylation of glycogen synthase converts enzyme to less active/b conformation
glycogen synthesis is inhibited when protein kinases are activated
what is the difference between the a and b form of an enzyme
a is the active form, independent of allosteric regulators and b is the enzyme dependant go local allosteric controls
what are the types of metabolic enzymes
catabolic reaction - phosphorylated form is its active one, opposite if involved in anabolic reaction
