lecture 4 Flashcards
steps of glycogen breakdown
broken down by phosphorylase to glucose-1-p to glucose-6-p to pyruvate
steps of production of glycogen
UDP-glucose to glycogen by glycogen synthase
OR
glucose to g-6-p to g-1-p to glycogen by phosophorylase
what is the role of glycogen phosphorylase in muscle
to provide ATP for muscle contraction
it is activated when ATP is in short supply, a muscle contracts and in a critical situation
what is generated by glycogen breakdown for glycolysis
g-6-p
how is glycogen phosphorylase allosterically regulated
glycogen phosphorlyase is activated by AMP
activation by amp is antagonised by atp and g-6-p
amp, atp and g6p dont bind the same site
allosteric regulation due to non covalent binding of a small molecule that binds to a site distinct from the active site
g6p is derived from the breakdown of glycogen and so is atp
g6p and atp are both classical feedback inhibitors of glycogen breakdown
what is the significance of phosphorylase activation by amp
amp is produced in many enzymatic reactions
major source is catalysed by adenylate kinase
it is a reversible reaction that uses very little free energy and it maintained close to equilibrium in most cells
if adp:atp ratio rises 2 fold, amp:atp rises 4 fold - effects of amp are antagonised by atp, phosphorylase is activated by increased amp:atp - a signal of low cellular energy status
glycogen is broken down to replenish atp when it is depleted
what does allosteric regulation maintain
homeostasis
how is allosteric mechanisms switched off
reverse the on function
constrained by the equilibrium constant for association:dissociation reaction
what are molecular switch mechanisms needed for
to cause a large change in signal output in response to a small change in signal input (large increase of AMP is needed to go from off to on)
molecular switched on and off pathways are different and usually involve covalent mods of proteins
adv of allosteric regulation
ligand binding site due to simple non covalent interaction = no enzyme is required
no energy directly consumed by association and dissociation of ligand
disadv of allosteric regulation
large changes in ligand conc required to achieve large effects
allosteric reg better for homeostasis than for making changes
adv of covalent modifications
interconversion reactions have high energy, must be catalysed by enzymes
for protein kinase reactions, equilibrium is driven by high cellular ratio of atp:adp
for protein phosphate reactions, equilibrium will always lie in favour of dephosphorylation - it is driven by high cellular water conc
small adjustments in relative activities of kinae and phosphate enzymes allow achievement of any desired ratio of protein:phosphoprotein from 0 to 1
protein phosphorylation is therefore good for switching cells from one state to another
disadv of covalent modifications
price paid for control of atp is consumed in the phosphorylation cycle
2 forms of phosphorylase
how are they two types found
b - allosterically activated by amp
a - doesnt require amp
a - phosphorylated at a single serine residue near n terminus
b - in dephosphorylated form
covalent mods of glycogen phosphorylase
phosphorylation is catalysed by a protein kinase ‘phosphorylase kinase’ which is activated by low calcium conc
muscle contractions triggered when stimulation of motor nerves trigger calcium release from sarcoplasmic reticulum of cell
glycogen breakdown is coupled with muscle contraction