BCOR 011 Lecture 12 9/28/2005ENZYMES. Last time… - G reaction “can” go spontaneous But when...
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Transcript of BCOR 011 Lecture 12 9/28/2005ENZYMES. Last time… - G reaction “can” go spontaneous But when...
What governs WHEN a reaction will occur?
The tower of blocks falling is favorablebut when will it happen?
Oxidation of carbohydrate polymers (starch)to carbon dioxide and water is favorablebut when will it happen?
Gasoline burning to carbon dioxide and wateris favorablebut when will it happen ?
For a Reaction to occur need to For a Reaction to occur need to Destabilize Existing StateDestabilize Existing Stateto to INPUT ENERGYINPUT ENERGY
Now In Transition
Potentialnet
usableenergy
Destabilizationenergy input“Activation
Energy”
Potentialnet
usableenergy
Need to INPUT ENERGY to Destabilize Existing State
In Transition After
Potentialnet
usableenergy
netusableenergy
released
RegainActivation
EnergyInvested
What does activation energy represent?
For a Reaction to Occur…
- reactants must find each other, - meet in proper orientation - and hit with sufficient force
Needs of Typical chemical reactions
- need large number of molecular collisions
- need collide violently enough to break pre-existing bonds (not bounce)
- need high concentration to find eachother at significant rate
HEAT !
The energy profile for an exergonic reaction
Fre
e en
ergy
Progress of the reaction
∆G < O
EA
Figure 8.14
A B
C D
Reactants
A
C D
B
Transition state
A B
C D
Products
ENZYMES make reactionseasier to occur at
reasonable temperatureby
LOWERING LOWERING the the ACTIVATION ENERGYACTIVATION ENERGY
EEAAof the reactionof the reaction
Activation EnergyEnergy necessary to overcome the status quo
G Thermodynamic“favorablility”
EA
“ease” of initiating reaction
G
EA
CATALYSTS:
promote a specific reactionBut are NOT consumed in the process
Key concepts:
Promotes - does not alter what would normally occur thermodynamically
Specificity - promotes only one reaction, only between specific reactants to give specific products
Reusable - regenerated in the process
How do Enzymes do it?
1. Enzymes have BINDING AFFINITYfor their reactants = Substrates
Brings substrates in close proximity: conc
Enzymes act as a Specific Platform
Have a very Specific 3-D Shape
With a Specific Arrangementof Functional Groups
FlexibleOH
HO
+
HO
PolarPolar
NonpolarNonpolar
ChargedCharged
Stabilized InteractionsStabilized Interactions
-
HO
OH
HO
OH
+
HO
OH
SPECIFICITYSPECIFICITY is the Key to Enzyme Action is the Key to Enzyme Action
ENZYMES:
Bind ONLY specific things
Bind them ONLY in a Specific 3-D Orientation
3a. Physical Strain3a. Physical Strain
3b.Chemical Strain3b.Chemical Strain
3. Enzymes cause BOND STRAINBOND STRAIN - destabilize existing bonds- destabilize existing bonds
““nutcracker effect”nutcracker effect”
The active site– Is the region on the enzyme where
the substrate binds
Figure 8.16
Substate
Active site
Enzyme
(a)
Enzyme-substrate interactions
Fischer: Lock & key
Koshland:Induced fit
3a. Physical bond strain3a. Physical bond strainDraw an quarter - an anvilDraw an quarter - an anvil
• The catalytic cycle of an enzyme
Substrates
Products
Enzyme
Enzyme-substratecomplex
1 Substrates enter active site; enzymechanges shape so its active siteembraces the substrates (induced fit).
2 Substrates held inactive site by weakinteractions, such ashydrogen bonds andionic bonds.
3 Active site (and R groups ofits amino acids) can lower EA
and speed up a reaction by• acting as a template for substrate orientation,• stressing the substrates and stabilizing the transition state,• providing a favorable microenvironment,• participating directly in the catalytic reaction.
4 Substrates are Converted intoProducts.
5 Products areReleased.
6 Active siteIs available fortwo new substrateMole.
Figure 8.17
3b. Chemical Bond Strain3b. Chemical Bond Straintease the bond to fall apart tease the bond to fall apart
CofactorsCofactors
• CofactorsCofactors– Are nonprotein enzyme helpers, eg
Zn++
• CoenzymesCoenzymes– Are organic cofactors
Non-polypeptide things at the active siteNon-polypeptide things at the active sitethat help enzymes do their jobthat help enzymes do their job
H+
OH-
H+
Partakes: but start and end with the same enzyme configPartakes: but start and end with the same enzyme config
Enzymes:
1. Bring reactants (substrates) in close proximity
2. Align substrates in proper orientation
3. Can act as a Lever: a press or an anvilsmall shape change translates to large force
4. Release products when reaction donerebind more substrates
5. Many small stepsMany small steps, each easily achievedrather than one huge leap
SUMMARY
You expect me to
JUMP this?
No ProblemDude
Enzymes carry out reactions in a series ofsmall steps rather than one energetic event
Reaction rates:
Example: H2O2-> H2O +O2
uncatalyzed –months
Fe+++ 30,000x faster
Catalase 100,000,000 x faster
Enzyme kinetics- kinetikos – moving
Rateor
velocityvelocity
# madeper min
Substrate Conc
maximum velocityVmax
1/2 V1/2 Vmaxmax
KKmm
“substrate affinity”
An enzyme catalyzed rxnAn enzyme catalyzed rxnCan be “saturated”Can be “saturated”
The lower the Klower the Kmm the betterthe enzyme recognizes substrate “finds it at low conc”
The higher the Vhigher the Vmaxmax the more substrate an enzyme can process per min (if substrate around)
“top speed”
“mpg”
Things that affect protein structureThings that affect protein structure often affect enzyme activityoften affect enzyme activity
temperature
pH
pH0 1 2 3 4 5 6 7 8 9 10
0 20 40 60 80 100 º C
Principal Ways of Regulating EnzymesPrincipal Ways of Regulating Enzymes
Competitive Competitive InhibitionInhibition
AllostericAllosteric Inhibition Inhibition
Covalent Modification (Covalent Modification (phosphorylationphosphorylation) )
-
HO
OH
HO
OH
+
HO
OH
HO
OH
CompetitiveInhibitors:
bind to active site “unproductively”and block true substrates’access
I
S1S2
S & I bind to same site
Allosteric Inhibitors“other” “site”
Distorts the conformation of the enzyme
Negativeallosteric regulator
Positive Positive allosteric regulators
Helps enzyme work betterpromotes/stabilizes an “active” conformation
Allosteric regulators Allosteric regulators change the shapechange the shapeconformationconformation of the enzyme of the enzyme
Stabilized inactiveform
Allosteric activaterstabilizes active fromAllosteric enyzme
with four subunitsActive site
(one of four)
Regulatorysite (oneof four)
Active formActivator
Stabilized active form
Allosteric activaterstabilizes active form
InhibitorInactive formNon-functionalactivesite
(a) Allosteric activators and inhibitors. In the cell, activators and inhibitors dissociate when at low concentrations. The enzyme can then oscillate again.
Oscillation
Figure 8.20