L8- Regulation of metabolic pathways Flashcards
where does glycolysis occur
in the cytoplasm of all tissues
how can glycolysis operate anaerobically
LDH
- production of NADH (reducing powers) meaning glycolysis can continue
- e.g. in RBC, muscles etc
allosteric means
other site
enzyme shave two sites
catalytic site
regulatory site
catalytic site
substrate binding
regulatory site
binding of specific regulatory molecules
- affects catalytic activity
- can activate or inhibit
allosteric regulation cause
covalent modification e.g. phosphorylation/ dephosphorylation
covalent modification e.g. phosphorylation/ dephosphorylation
alters protein conformation and therefore activity
pathways are regulated by
irreversible steps
with irreversible steps reduced activity reduces the rate of flow of..
substrates through the pathway directly, reducing levels of product
with reversible steps, even when inhibited
reactions still come to equilibrium so levels of product unaffected
product inhibition
where the product displaces the equilibrium towards the substrate
- reduces rate of catalysis of substrate to product
feedback inhibitor
where final product inhibits first enzyme in pathway
- reduces entry of substrate into the pathway leading to build up of intermediates
committing step
inhibition of committing step allows substrate to be diverted into other pathways
regulation of enzymes can be
inhibitory or stimulatory
catabolic pathways such as glycolysis and the kerb cycle are inhibited
by high energy signals such as ATP, NADH and FAD2H
catabolic pathways such as glycolysis and the kerb cycle are stimulated by
low energy signals such as o ADP, AMP, NAD+, FAD+
hormonal regulation
hormone receptor binding can activate signalling pathways e.g. insulin (tyrosine kinase receptor)
- this can activate Protein kinases (phosphorylation) or phosphates (dephosophorylation)
phosphorylation/ dephospho rylation of target enzyme
alters protein conformation/ activity positively or negatively depending on the target enzyme
example of phosphorylation: adrenaline
adrenaline binds to GPCR
o Activates protein kinase A
o Phosphorylation activates phosphorylase kinase
o Phosphorylation of glycogen phosphorylase
i. Stimulates glycogen break down
example of phosphorylation: insulin
Insulin binds to TK receptor
o Stimulated signalling pathway activates protein phosphatase 1
o Dephosphorylates/activates pyruvate dehydrogenase
i. Stimulates glucose utilisation
o Dephosphorylates glycogen phosphorylase
i. Inhibits glycogen breakdown
feed forward
- Early pathway substrate provides positive allosteric signal to stimulate a later enzyme to activate the pathway
name the 3 key regulators of glycolysis
- Hexokinase (glucokinase in the liver) (1)
- Phosphofructokinase-1 (3)
- Pyruvate kinase (10)
hexokinase
Product inhibition by Glucose-6-P
Enzyme activity will reduce as more glucose is catalysed to glucose-6-p- negative regulator
phosphofructokinase-1 (PFK) is the most
important enzyme in the regulation of glycolysis
how can PFK regulate glycolysis
allosteric regulation (muscle)
hormonal regulation (liver)
PFK and allosteric regulation (muscle)
o Inhibited by high ATP
o Stimulated by high AMP
PFK and hormonal regulation (liver)
o Stimulated by insulin
o Inhibited by glucagon
Pyruvate kinase
regulated via phosphoregulaton
- final stage of glycolysis
when glucagon (starvation hormone) binds to its receptor
protein kinase A conc in the cell increases and this phosphorylated ADP–> ATP ( low energy signal)
-INHIBITING GLYCOLYSIS
when insulin (well fed hormone) binds to it receptor
protein phosphatase 1 conc increases and this dephosphorylates ATP–> ADP (high energy signal)
- STIMUALTING GLYCOLYSIS
hexokinase is inhibited by
glucose-6-phosphate (its own product) - therefore PRODUCT INHIBITION
high ATP ……. PFK
inhibits
high AMP ……. PFK
stimulates
where is the commuting step in glycolysis
phosphofructokinase
high insulin and low glucagon will
stimulate glycolysis by causing enzyme depths (more high energy signals such as ADP)
