Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Concept 8.4: Enzymes speed up metabolic reactions by lowering energy barriers

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

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SucroseC12H22O11

GlucoseC6H12O6

FructoseC6H12O6


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

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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


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

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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


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

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Substrate

Active site

Enzyme Enzyme-substratecomplex


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

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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.


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


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

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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


Cofactors

• Cofactors are nonprotein enzyme helpers

• Coenzymes are organic cofactors


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.


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


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


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

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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


• 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

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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


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

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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)


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

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Mitochondria,sites of cellular respiration

1 µm

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Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings Concept 8.4: Enzymes speed up metabolic reactions by lowering energy barriers