Topic 8: Regulatory mechanisms Flashcards
what are the different short term regulatory mechanisms
- different enzyme forms - isoenzymes
- change in enzyme conformation - allosteric regulation
- reversible covalent modification - phosphorylation
- proteolytic activation
- controlling amount of enzyme present - gene expression
what are isoenzymes
enzymes that catalyse the same reaction but have different amino acid sequence so different activity and regulatory properties
synthesised from a different gene or differentially spliced from the same gene
what are examples of isoenzymes
hexokinase (high KM)
glucokinase (low KM)
both catalyse phosphorylation of glucose
what are some features of allosteric regulation
the enzymes usually action at a distance
can exist in 2 forms: T state = low affinity, R state = high affinity, sigmoidal reaction curve when both states combined
usually multi subunit proteins
how can the different enzyme conformations regulate
allosteric regulation results due to changes in enzyme concentration
Activators - increase the proporion of enzyme in the high affinity form so stabilise R state, shift curve to left
inhibitors - increase the proportion of enzyme in the low affinity form so stabilise T stafem shift curve to right
what is an example of an enzyme involved in allosteric regulation
phophofructokinase - 1
activators - AMP, fructose 2,6-bisphosphate
inhibitors - citrate, ATP, H+
how does reversible covalent modification work
protein kinases - transfer phosphate from ATP to OH group of amino acid residues (ser, thr, tyr)
protein phosphatases - reverse effects of kinases by catalysing hydrolytic removal of phosphoryl groups from proteins
why is protein phosphorylation so effective
the free energy of phosphorylation is large (ATP)
adds 2 negative charges
a phosphoryl group can make H bonds
rate of phosphorylation/de can be changed by changing enzymes - fine tuned
links energy status of the cell to metabolism through ATP
allow for amplification effects - cascade like mechanism
how does amplification work in reversible covalent modification
when enzymes activate enzymes, the number of affected molecules increase geometrically in an enzyme cascade
3 enzymes - 9 fold amplification
what is proteolytic activation
involves inactive precursor molecules - zymogens or proenzymes
involves breaking of peptide bond which will remove pro segment making them active
irreversible
what are examples of proteolytic activation
blood clotting
digestive enzymes
apoptosis
^ important when processes need to be tightly controlled
what is an example of a zymogen used in proteolytic activation
pancreatic zymogens - breakdown of dietary food stuff
important it is only active when released from cell
trypsingogen -> trypsin which stimulate activation of other zymogen enzymes which are secreted from the pancreas
