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Transcript of F REE E NERGY AND M ETABOLISM The concept of free energy can be applied to the chemistry of life’s...
FREE ENERGY AND METABOLISM
The concept of free energy can be applied to the chemistry of life’s processes
© 2011 Pearson Education, Inc.
EXERGONIC AND ENDERGONIC REACTIONS IN METABOLISM
An exergonic reaction proceeds with a net release of free energy and is spontaneous
An endergonic reaction absorbs free energy from its surroundings and is nonspontaneous
© 2011 Pearson Education, Inc.
FIGURE 8.6 (a) Exergonic reaction: energy released, spontaneous
(b) Endergonic reaction: energy required, nonspontaneous
Reactants
EnergyProducts
Progress of the reaction
Amount of energy
released(G 0)
ReactantsEnergy
Products
Amount of energy
required(G 0)
Progress of the reaction
Fre
e e
ne
rgy
Fre
e e
ne
rgy
FIGURE 8.6A
(a) Exergonic reaction: energy released, spontaneous
Reactants
EnergyProducts
Progress of the reaction
Amount of energy
released(G 0)
Fre
e en
erg
y
FIGURE 8.6B
(b) Endergonic reaction: energy required, nonspontaneous
ReactantsEnergy
Products
Amount of energy
required(G 0)
Progress of the reaction
Fre
e en
erg
y
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
© 2011 Pearson Education, Inc.
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 thermal energy that the reactant molecules absorb from their surroundings
© 2011 Pearson Education, Inc.
FIGURE 8.12
Transition state
Reactants
Products
Progress of the reaction
Fre
e e
ner
gy EA
G O
A B
C D
A B
C D
A B
C D
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
© 2011 Pearson Education, Inc.
FIGURE 8.13
Course ofreactionwithoutenzyme
EA
withoutenzyme EA with
enzymeis lower
Course ofreactionwith enzyme
Reactants
Products
G is unaffectedby enzyme
Progress of the reaction
Fre
e en
erg
y
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
© 2011 Pearson Education, Inc.
CATALYSIS IN THE ENZYME’S ACTIVE SITE
In an enzymatic reaction, the substrate binds to the active site of the enzyme
The active site can lower an EA barrier by Orienting substrates correctly Straining substrate bonds Providing a favorable microenvironment Covalently bonding to the substrate
© 2011 Pearson Education, Inc.
FIGURE 8.15-1
Substrates
Substrates enter active site.
Enzyme-substratecomplex
Substrates are heldin active site by weakinteractions.
12
Enzyme
Activesite
FIGURE 8.15-2
Substrates
Substrates enter active site.
Enzyme-substratecomplex
Substrates are heldin active site by weakinteractions.
Active site canlower EA and speedup a reaction.
12
3
Substrates areconverted toproducts.
4
Enzyme
Activesite
FIGURE 8.15-3
Substrates
Substrates enter active site.
Enzyme-substratecomplex
Enzyme
Products
Substrates are heldin active site by weakinteractions.
Active site canlower EA and speedup a reaction.
Activesite is
availablefor two new
substratemolecules.
Products arereleased.
Substrates areconverted toproducts.
12
3
45
6
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
© 2011 Pearson Education, Inc.
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
Optimal conditions favor the most active shape for the enzyme molecule
© 2011 Pearson Education, Inc.
FIGURE 8.16
Optimal temperature fortypical human enzyme (37°C)
Optimal temperature forenzyme of thermophilic
(heat-tolerant)bacteria (77°C)
Temperature (°C)(a) Optimal temperature for two enzymes
Ra
te o
f re
ac
tio
nR
ate
of
rea
cti
on
120100806040200
0 1 2 3 4 5 6 7 8 9 10pH
(b) Optimal pH for two enzymes
Optimal pH for pepsin(stomachenzyme)
Optimal pH for trypsin(intestinal
enzyme)
FIGURE 8.16A
Optimal temperature fortypical human enzyme (37°C)
Optimal temperature forenzyme of thermophilic
(heat-tolerant)bacteria (77°C)
Temperature (°C)(a) Optimal temperature for two enzymes
Rat
e o
f re
acti
on
120100806040200
FIGURE 8.16B
Rat
e o
f re
acti
on
0 1 2 3 4 5 6 7 8 9 10pH
(b) Optimal pH for two enzymes
Optimal pH for pepsin(stomachenzyme)
Optimal pH for trypsin(intestinal
enzyme)
IB QUESTIONS?
3.6.1 Define enzyme and active site3.6.2 Explain enzyme-substrate specificity.3.6.3 Explain the effects of temperature, pH and substrate concentration on enzyme activity.3.6.4 Define denaturation.3.6.5 Explain the production of lactase in the production of lactose free milk.
COFACTORS
Cofactors are nonprotein enzyme helpers Cofactors may be inorganic (such as a metal
in ionic form) or organic An organic cofactor is called a coenzyme Coenzymes include vitamins
© 2011 Pearson Education, Inc.
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
Examples of inhibitors include toxins, poisons, pesticides, and antibiotics
© 2011 Pearson Education, Inc.
FIGURE 8.17
(a) Normal binding (b) Competitive inhibition (c) Noncompetitive inhibition
Substrate
Activesite
Enzyme
Competitiveinhibitor
Noncompetitiveinhibitor
THE EVOLUTION OF ENZYMES
Enzymes are proteins encoded by genes Changes (mutations) in genes lead to
changes in amino acid composition of an enzyme
Altered amino acids in enzymes may alter their substrate specificity
Under new environmental conditions a novel form of an enzyme might be favored
© 2011 Pearson Education, Inc.
FIGURE 8.18
Two changed amino acids werefound near the active site.
Active site
Two changed amino acidswere found in the active site.
Two changed amino acidswere found on the surface.
CONCEPT 8.5: REGULATION OF ENZYME ACTIVITY HELPS CONTROL METABOLISM
Chemical chaos would result if a cell’s metabolic pathways were not tightly regulated
A cell does this by switching on or off the genes that encode specific enzymes or by regulating the activity of enzymes
© 2011 Pearson Education, Inc.
ALLOSTERIC REGULATION OF ENZYMES
Allosteric regulation may either inhibit or stimulate an enzyme’s activity
Allosteric regulation occurs when a regulatory molecule binds to a protein at one site and affects the protein’s function at another site
© 2011 Pearson Education, Inc.
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
© 2011 Pearson Education, Inc.
FIGURE 8.19
Regulatorysite (oneof four)
(a) Allosteric activators and inhibitors
Allosteric enzymewith four subunits
Active site(one of four)
Active form
Activator
Stabilized active form
Oscillation
Non-functionalactive site
Inactive formInhibitor
Stabilized inactiveform
Inactive form
Substrate
Stabilized activeform
(b) Cooperativity: another type of allosteric activation
FIGURE 8.19A
Regulatory site (one of four)
(a) Allosteric activators and inhibitors
Allosteric enzymewith four subunits
Active site(one of four)
Active form
Activator
Stabilized active form
Oscillation
Nonfunctionalactive site
Inactive formInhibitor
Stabilized inactive form
FIGURE 8.19B
Inactive form
Substrate
Stabilized activeform
(b) Cooperativity: another type of allosteric activation
Cooperativity is a form of allosteric regulation that can amplify enzyme activity
One substrate molecule primes an enzyme to act on additional substrate molecules more readily
Cooperativity is allosteric because binding by a substrate to one active site affects catalysis in a different active site
© 2011 Pearson Education, Inc.
IDENTIFICATION OF ALLOSTERIC REGULATORS
Allosteric regulators are attractive drug candidates for enzyme regulation because of their specificity
Inhibition of proteolytic enzymes called caspases may help management of inappropriate inflammatory responses
© 2011 Pearson Education, Inc.
FIGURE 8.20
Caspase 1 Activesite
Substrate
SH SH
SH
Known active form Active form canbind substrate
Allostericbinding site
Allostericinhibitor
Hypothesis: allostericinhibitor locks enzymein inactive form
Caspase 1
Active form Allostericallyinhibited form
Inhibitor
Inactive form
EXPERIMENT
RESULTS
Known inactive form
FIGURE 8.20A
Caspase 1 Activesite
Substrate
SH SH
SH
Known active form Active form canbind substrate
Allostericbinding site
Allostericinhibitor
Hypothesis: allostericinhibitor locks enzymein inactive form
EXPERIMENT
Known inactive form
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
© 2011 Pearson Education, Inc.
FIGURE 8.21
Active siteavailable
Isoleucineused up bycell
Feedbackinhibition
Active site ofenzyme 1 isno longer ableto catalyze theconversionof threonine tointermediate A;pathway isswitched off. Isoleucine
binds toallostericsite.
Initial substrate(threonine)
Threoninein active site
Enzyme 1(threoninedeaminase)
Intermediate A
Intermediate B
Intermediate C
Intermediate D
Enzyme 2
Enzyme 3
Enzyme 4
Enzyme 5
End product(isoleucine)
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
In eukaryotic cells, some enzymes reside in specific organelles; for example, enzymes for cellular respiration are located in mitochondria
© 2011 Pearson Education, Inc.