Lecture 6 Flashcards
Define mobilisation
In time of metabolic need, cells switch on the breakdown of stored glycogen very rapidly using a combination of signals
Describe glycogen breakdown in muscle
Glycogen->Gluc-1-phosphate->Gluc-6-phosphate->Pyruvate
Pyruvate->Lactate
Pyruvate->Co2
Describe Glycogen breakdown in the liver
Glycogen->Gluc-1-phosphateGluc-6-phosphate->glucose using glucose-6-phosphatase
Describe degradation
Phosphorylase can only break α-1,4 links up to within 4 glucose units from a branch point
Transferase activity of the debranching enzyme removes 3 residues from the branch and transfers them to the end of another chain in α-1,4-linkage
The single glucose unit left at the branch is removed by the action of the α-1,6-glucosidase activity of the debranching enzyme
The chain can then be broken down by phosphorylase until it meets the next branch point.
Describe glycogen synthesis
Glucose->Glucose-6-phospahte using ATP, HK/Glucokinase (liver)
Glucose-6-phosphate->glucose-1-phosphate
Glucose-1-phophate->UDP-glucose using UTP
Glycogen(n)->Glycogen(n+1) using glycogen synthase resulting in UDP as a side product.
how does glycogen synthesis start?
Glycogen synthase can add glucose units only to a pre-existing chain of more than four glucosyl residues
The priming function is carried out by a protein, glycogenin
UDP-glucose donates the first glucosyl residue and attaches it to the amino acid tyrosine in the glycogenin
The remaining glucose units are added in an α-1,4-linkage from UDP-glucose to create a growing chain
Describe the introduction of branches for glycogen
Glycogen synthase extends the chain in α1,4-linkages but cannot make branches
Branching enzyme transfers a block of 7 residues from a growing chain to create a new branch with an α1,6-linkage
The new branch must not be within 4 residues of a pre-existing branch
Describe the allosteric regulation of phosphorylase
Glycogen phosphorylase in muscle is subject to allosteric regulation by AMP, ATP and glucose-6-phosphate
AMP (present when ATP is depleted during muscle contraction) activates phosphorylase
ATP and glucose-6-phosphate, which both compete with AMP binding, inhibit phosphorylase. They are signs of high energy levels.
Thus glycogen breakdown is inhibited when ATP and glucose-6-phosphate are plentiful
Describe the allosteric regulation of glycogen synthase
Glycogen synthase is allosterically activated by glucose-6-phosphate (the opposite to the effect on phosphorylase)
Thus glycogen synthesis is activated when glucose-6-phosphate is plentiful.
The cell is programmed to store glucose as glycogen when the input to glycolysis (glucose-6-phosphate), and the product of glycolysis (ATP) are present
Explain the regulation of glycogen metabolism by covalent modification
Mediated by the addition (and removal) of a phosphate group
Addition of a phosphate group is known as phosphorylation and is catalysed by protein kinases
This is a reversible modification; removal of phosphate groups (dephosphorylation) is catalysed by protein phosphatases
Explain cAMP-dependent phosphorylation
The cAMP cascade results in phosphorylation of a serine hydroxyl of muscle glycogen phosphorylase, which promotes transition to the active state
The phosphorylated enzyme is less sensitive to allosteric inhibitors, thus even if cellular ATP levels and glucose-6- phosphate are high, phosphorylase will be activated
Describe the reciprocal regulation of phosphorylase and glycogen synthase
The inactive form of glycogen synthase is the phosphorylated form.
Therefore, an increase in protein phosphatase will increase the activity of glycogen synthase.
Similarly, the active form of phosphorylase is the phosphorylated form. Therefore, any increase in activity of protein kinase will increase the activity of phosphorylase.
