Human Function 6 Flashcards
(34 cards)
Reaction involving glycogen phosphorylase
Pi breaks bond in glycogen to make G1P –> G6P –> ATP
Mechanisms for regulating enzyme activity
1) change amount of enzyme
2) noncovalent modulation through allosteric interactions
3) covalent modifications (irreversible and reversible)
4) genetic variation
Glycogen phosphorylase structure
- dimer of equal subunits
- active site
- allosteric site binding G6P, ATP, AMP
- serine that can be phosphorylated
Curve of v vs Pi for glycogen phosphorylase
Sigmoidal
Shows positive cooperativity
Feedback inhibition involving glycogen phosphorylase
If have enough ATP or G6P, they can bind to regulatory site of enzyme so it can’t bind glycogen (and break it down for ATP).
* ensures that glycogen is not used if not needed
What does binding of G6P or ATP do to the v vs Pi curve for glycogen phosphorylase?
Shifts curve right
Decreases v0 for a given amount of Pi (decreases conversion of glycogen to ATP)
Increases Km (the concentration of Pi at 1/2 v max) (Pi not used as much to convert to ATP because there is already enough ATP)
Allosteric activation of glycogen phosphorylase done by…
Activated by AMP
AMP level goes up when ATP goes down - so AMP signals to make more ATP
What does presence of AMP do to the v vs Pi curve?
Shifts curve to left
Increases v0
Decreases Km
Covalent modification of glycogen phosphorylase by reversible phosphorylation
Adding Pi to activates enzyme
Removing Pi deactivates enzyme
Isozymes
Catalyze same reaction
Different structure &kinetics
Coded by different genes
Differences of glucokinase isozyme from other isozymes of hexokinase
- higher Km
- positive cooperativity/sigmoidal (others are hyperbolic)
- only active at high [glucose] and responds to changing [glucose]
Function of glucokinase
Control glucose use by the liver
Glucose and glucokinase activity after meal
Glucose from blood to liver increases
Glucokinase activity increases - tells liver to use glucose to make glycogen
Glucose and glucokinase between meals
Glucose low (no import of glucose from blood to liver) Glucokinase activity drops - signals liver to export glucose
Which CPK isozyme is used to monitor myocardial infarctions and why?
CPK MB or CPK2
Localized in heart tissues
Normally none in blood (but present after myocardial infarction)
What aspect of LDH do you have to monitor to show myocardial infarction?
LDH1/LDH2 ratio
If >1, that means pushing out more heart isozymes than muscle isozymes
Which is more sensitive? CPK2 levels or LDH1/LDH2 ratio?
CPK2 levels
Reversible noncovalent competitive inhibition
Competitive inhibitor is substrate or intermediate analog
Binds to active site and prevents substrate binding by forming inactive EI complex
Reversible - can be overcome by incr [S]
No chemistry is done by enzyme on inhibitor
Km increases
Vmax same
Km and Vmax of competitive inhibition
Km increases
Vmax same
Irreversible enzyme inactivation
Active site is covalently modified by inhibitor
Suicide inactivator (a type of irreversible enzyme inactivation)
Acts like a substrate: binds to active site and enzyme begins catalysis
Molecule covalently attaches to active site, destroying enzyme activity
Has high specificity because only enzyme can convert inhibitor to a modifying inactivator
Function of NSAIDS like aspirin and ibuprofen
Inhibit conversion of arachidonic acid to prostaglandins and thromboxanes by targeting the enzyme that does conversion, COX
Aspirin has similar structural features as the COX substrate and product, which are…
COO-
C=C
Hydrocarbon ring
O’s
How aspirin inactivates COX
Binds covalently to COX which inactivates it (so prostaglandins which signal inflammation and pain won’t be produced)
