Lecture 24- enzyme regulation Flashcards
Why are enzymes regulated?
To increase or decrease activity
Maintain metabolic effectiveness and avoids waste
The slowest (rate limiting) step of a metabolic pathway is the most…..
efficient control point of the pathway
How are rate limiting enzymes controlled?
By mechanisms that affect the catalytic site
Regulatory mechanisms of enzymes:
Allosteric activation/inhibition
Phosphorylation (or other covalent modification)
Protein-protein interactions
Proteolytic cleavage
Allosteric regulation
Activity modulation via reversible, non-covalent binding of small molecules
Bind at allosteric site
Allosteric enzymes are ofter composed of ….
Multiple subunits
Allosteric effector binding…
changes catalytic site conformation
(affects substrate binding)
Advantages of allosteric regulation
Effectors as the bind to sites other than catalytic site
Can be activators (not just inhibitors)
Effectors don’t need to resemble substrate or product
Regulation is rapid
if enzyme activity increases when the effete binds then…
it is an allosteric activator/positive effector
Allosteric regulation affects …. and …
Enzyme affinity for substrate and/or maximal catalytic activity
Homotropic effectors
The substrate serves as an allosteric effector
Heterotrophic effector
The effector is different from the substrate
(eg. citrate: -ve effector for phosphofuctokinas- 1, important enzyme for glycolosis)
Co-operativity
A homographic effector functions as a positive effector
Positive co-operativity
When a substrate binds one subunit it can enhance the catalytic properties of the other subunits
Negative co-operativity
Some substrates bind a subunit and it can reduce the catalytic properties of other subunits
The concerted model
1st substate molecule has difficulty binding as all subunits in T state
All change to R state
All subunits exist in the same conformation
The sequential model
Enzyme/protein molecule affinity is relative and changes as substrates bind
When substrate binds, molecules goes from T-state to R-state
Covalent modification- enzyme regulation
Lead to conformational changes
eg.phosphorylation- addition of phosphate groups- mediated by ‘protein kinases’
Phosphate groups are removed by protein phosphates via hydrolysis
Protein kinases
Some protein kinases only regulate one protein, others simultaneously regulate several rate-limiting factors
Adrenaline …. the intracellular concentration of 3’,5’-cyclic AMP (cAMP)
increases
Covalent modification examples
Addition/ removal of acetyl , ADP-Ribose to lipids
Protein-protein interactions
Direct interactions between proteins can lead to conformation changes in the active site
eg. calcium-calm odium family of modulator proteins-modulates the activity of glycogen phosphorylase kinase
eg. G-proteins- contain an internal clock that slowly hydrolyses GTP
Proteolytic cleavage
Enzymes can be irreversibly activated or inactivated by proteolytic enzymes
Degradation of enzymes by intracellular proteases on lysosomes or proteasomes determines enzymatic activity over a longer period
Enzyme synthesis
Control of enzymatic activity can be made here
Induction/repression leads to an alteration in total population of active sites
This type of regulation often only needed at one point of development or under selected physiologic conditions
