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

LE 8-13

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

LE 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

Free

ene

rgy


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 8-15

Course ofreactionwithoutenzyme

EA

without enzyme

DG is unaffectedby enzyme

Progress of the reaction

Free

ene

rgy

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

LE 8-16

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

LE 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.


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

LE 8-18Optimal 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

Rat

e of

reac

t ion

Optimal pH for pepsin(stomach enzyme)

Optimal pHfor trypsin(intestinalenzyme)

pHOptimal pH for two enzymes

0

Rat

e of

r eac

t ion

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 8-19Substrate

Active site

Enzyme

Competitiveinhibitor

Normal binding

Competitive inhibition

Noncompetitive inhibitorNoncompetitive 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

LE 8-20a

Allosteric enzymewith four subunits

Regulatorysite (oneof four) Active form

ActivatorStabilized active form

Active site(one of four)

Allosteric activatorstabilizes active form.

Non-functionalactive site

Inactive form Inhibitor 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

LE 8-20b

Substrate

Binding of one substrate molecule toactive site of one subunit locks allsubunits in active conformation.

Cooperativity another type of allosteric activationStabilized 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

LE 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)


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 8-22

Mitochondria,sites of cellular respiration

1 µm

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Concept 8.4: Enzymes speed up metabolic reactions by lowering energy barriers

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