Lecture 3.5: Enzyme Regulation Flashcards
Regulation of enzyme activity is mediated by:
- RNA synthesis
- RNA processing
- Protein synthesis
- Protein targeting
- Protein degredation
- binding of regulatory molecules
- covalent modification
- proteolytic processing
Allosteric Regualtion
2 active sites
do not conform to michaelis-menten kinetics
Allosteric effectors (modulators) bind to specific [ ] sites and [ ]
regulatory (allosteric)
alter enzyme acitivty
Allosteric activators trends
curve shifts left
increased binding affinity
may stimulate activity
Allosteric inhibitors
curve shifts right
decreased binding affinity
may decrease activity
ATCase catalyzes first step in [ ]
pyrimidine biosynthesis
ATCase displays a [ ] curve
sigmoidal
ATCase substrates?
Carbamoyl phosphate
L-aspartate
ATCase inhibitor?
cytidine-triphosphate (CTP)
ATCase activator?
ATP
CTP affects on ATCase
CTP is not structurally similar to substrate so allosteric inihibitor
Decreases activity of ATCase
binds to regulatory subunits and stabilizes T state
shifts curve right
ATP on ATCase
Increases activity of ATCase
binds to regulatory subunits and stabilizes R state
shifts curve left
ATCase is composed of [ ] protein complexes forming the functional [ ] complex
Two C3R3 trimeric protein complexes
C6R6 ATCase complex
When ATCase is in its R-state what happens?
increased distance between the catalytic trimers
covalent modifications
reversible modifications that can rapidly regualte catalytic efficiency of enzymes
* Phophorylation
* Adenylylation
Phosphorylation
is catalyzed by kinase and requires the expenditure of ATP
amino acids involved in phosphorylation
serine
threonine
tyrosine
histidine can be phosphorylated but its too fast
Phosphatase
catalyzes cleavage of phosphate ester bond with water
removal of phosphoryl group
Phosphorylation-dephosphorylation results in a what structural and chemical changes
addition of negative charges changes electrostatic interactions and conformation
phosphoryl group can form H-bonds
Glycogen phosphorylase regulated by?
by phosphorylation in response to hormone signaling
Glucagon and Epinephrine role on glycogen phosphorylase
low levels of glucose = glucagon
glucagon + epinephrine stimulate phosphorylase kinase to activate glycogen phosphorylase
addition of ATP further stimulates
Insulin roles on glycogen phosphorylase
high level of glucose = insulin
insulin stimulates protein phosphatase 1 to deactivate glycogen phosphorylase
addition of water further deactivates
Insulin roles on glycogen phosphorylase
high level of glucose = insulin
insulin stimulates protein phosphatase 1 to deactivate glycogen phosphorylase
addition of water further deactivates
proteolytic processing is an [ ] process
irreversible
zymogens
inactive precursor enzymes
* trypsinogen
* chymotrypsinogen
* protoelastase
* procarboxy-peptidase
* prolipase
most pancreatic proteases are synthesized as [ ]
inactive precursors
proteolytic cleavage can [ ] enzymes
activate
removal of amino acid segment generates the active enzyme
Chymotrypsin is activated by [ ]
proteolytic cleavage
1. chymotrypsinogen is cleaved by trypsin
2. two π chymotrypsin segments are formed from the cleavage between L13 and S14 + R15 and I16 & Y146 and T147 + N148 and A149
chymotrypsin is stabilized by disulfide bonds
