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Transcript of Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Concept 8.4: Enzymes speed...
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Concept 8.4: Enzymes speed up metabolic reactions by lowering energy barriers
• A catalyst is a chemical agent that speeds up a reaction without being consumed by the reaction
• An enzyme is a catalytic protein
• Hydrolysis of sucrose by the enzyme sucrase is an example of an enzyme-catalyzed reaction
LE 8-13LE 8-13
SucroseC12H22O11
GlucoseC6H12O6
FructoseC6H12O6
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
The Activation Energy Barrier
• Every chemical reaction between molecules involves bond breaking and bond forming
• The initial energy needed to start a chemical reaction is called the free energy of activation, or activation energy (EA)
• Activation energy is often supplied in the form of heat from the surroundings
LE 8-14LE 8-14
Transition state
C D
A B
EA
Products
C D
A B
DG < O
Progress of the reaction
Reactants
C D
A B
Fre
e en
erg
y
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
How Enzymes Lower the EA Barrier
• Enzymes catalyze reactions by lowering the EA barrier
• Enzymes do not affect the change in free-energy (∆G); instead, they hasten reactions that would occur eventually
Animation: How Enzymes Work
LE 8-15LE 8-15
Course ofreactionwithoutenzyme
EA
without enzyme
DG is unaffectedby enzyme
Progress of the reaction
Fre
e en
erg
y
EA withenzymeis lower
Course ofreactionwith enzyme
Reactants
Products
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Substrate Specificity of Enzymes
• The reactant that an enzyme acts on is called the enzyme’s substrate
• The enzyme binds to its substrate, forming an enzyme-substrate complex
• The active site is the region on the enzyme where the substrate binds
• Induced fit of a substrate brings chemical groups of the active site into positions that enhance their ability to catalyze the reaction
LE 8-16LE 8-16
Substrate
Active site
Enzyme Enzyme-substratecomplex
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Catalysis in the Enzyme’s Active Site
• In an enzymatic reaction, the substrate binds to the active site
• The active site can lower an EA barrier by
– Orienting substrates correctly
– Straining substrate bonds
– Providing a favorable microenvironment
– Covalently bonding to the substrate
LE 8-17LE 8-17
Enzyme-substratecomplex
Substrates
Enzyme
Products
Substrates enter active site; enzymechanges shape so its active siteembraces the substrates (induced fit).
Substrates held inactive site by weakinteractions, such ashydrogen bonds andionic bonds.
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.
Substrates areconverted intoproducts.
Products arereleased.
Activesite is
availablefor two new
substratemolecules.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Effects of Local Conditions on Enzyme Activity
• An enzyme’s activity can be affected by:
– General environmental factors, such as temperature and pH
– Chemicals that specifically influence the enzyme
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Effects of Temperature and pH
• Each enzyme has an optimal temperature in which it can function
• Each enzyme has an optimal pH in which it can function
LE 8-18LE 8-18
Optimal temperature fortypical human enzyme
Optimal temperature forenzyme of thermophilic (heat-tolerant bacteria)
Temperature (°C)
Optimal temperature for two enzymes
0 20 40 60 80 100
Ra
te o
f re
ac
tio
n
Optimal pH for pepsin(stomach enzyme)
Optimal pHfor trypsin(intestinalenzyme)
pH
Optimal pH for two enzymes
0
Ra
te o
f re
ac
tio
n
1 2 3 4 5 6 7 8 9 10
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Cofactors
• Cofactors are nonprotein enzyme helpers
• Coenzymes are organic cofactors
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Enzyme Inhibitors
• Competitive inhibitors bind to the active site of an enzyme, competing with the substrate
• Noncompetitive inhibitors bind to another part of an enzyme, causing the enzyme to change shape and making the active site less effective
LE 8-19LE 8-19Substrate
Active site
Enzyme
Competitiveinhibitor
Normal binding
Competitive inhibition
Noncompetitive inhibitor
Noncompetitive inhibition
A substrate canbind normally to the
active site of anenzyme.
A competitiveinhibitor mimics the
substrate, competingfor the active site.
A noncompetitiveinhibitor binds to the
enzyme away from theactive site, altering the
conformation of theenzyme so that its
active site no longerfunctions.
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Concept 8.5: Regulation of enzyme activity helps control metabolism
• Chemical chaos would result if a cell’s metabolic pathways were not tightly regulated
• To regulate metabolic pathways, the cell switches on or off the genes that encode specific enzymes
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Allosteric Regulation of Enzymes
• Allosteric regulation is the term used to describe cases where a protein’s function at one site is affected by binding of a regulatory molecule at another site
• Allosteric regulation may either inhibit or stimulate an enzyme’s activity
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Allosteric Activation and Inhibition
• Most allosterically regulated enzymes are made from polypeptide subunits
• Each enzyme has active and inactive forms
• The binding of an activator stabilizes the active form of the enzyme
• The binding of an inhibitor stabilizes the inactive form of the enzyme
LE 8-20aLE 8-20a
Allosteric enzymewith four subunits
Regulatorysite (oneof four) Active form
Activator
Stabilized active form
Active site(one of four)
Allosteric activatorstabilizes active form.
Non-functionalactive site
Inactive formInhibitor
Stabilized inactive form
Allosteric inhibitorstabilizes inactive form.
Oscillation
Allosteric activators and inhibitors
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
• Cooperativity is a form of allosteric regulation that can amplify enzyme activity
• In cooperativity, binding by a substrate to one active site stabilizes favorable conformational changes at all other subunits
LE 8-20bLE 8-20b
Substrate
Binding of one substrate molecule toactive site of one subunit locks allsubunits in active conformation.
Cooperativity another type of allosteric activation
Stabilized active formInactive form
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Feedback Inhibition
• In feedback inhibition, the end product of a metabolic pathway shuts down the pathway
• Feedback inhibition prevents a cell from wasting chemical resources by synthesizing more product than is needed
LE 8-21LE 8-21
Active siteavailable
Initial substrate(threonine)
Threoninein active site
Enzyme 1(threoninedeaminase)
Enzyme 2
Intermediate A
Isoleucineused up bycell
Feedbackinhibition Active site of
enzyme 1 can’tbindtheoninepathway off
Isoleucinebinds toallostericsite
Enzyme 3
Intermediate B
Enzyme 4
Intermediate C
Enzyme 5
Intermediate D
End product(isoleucine)
Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Specific Localization of Enzymes Within the Cell
• Structures within the cell help bring order to metabolic pathways
• Some enzymes act as structural components of membranes
• Some enzymes reside in specific organelles, such as enzymes for cellular respiration being located in mitochondria
LE 8-22LE 8-22
Mitochondria,sites of cellular respiration
1 µm