Prevention of Infection Chapter 8 Chapter 8: Infection Prevention1.
Chapter 8
description
Transcript of Chapter 8
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PowerPoint Lectures for Biology, Seventh Edition
Neil Campbell and Jane Reece
Lectures by Chris Romero
Chapter 8
An Introduction to Metabolism
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An organism’s metabolism transforms matter and energy, subject to the laws of thermodynamics
• Metabolism is the totality of an organism’s chemical reactions
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Organization of the Chemistry of Life into Metabolic Pathways
• A metabolic pathway begins with a specific molecule and ends with a product
• Each step is catalyzed by a specific enzyme
LE 8-UN141
Enzyme 1
A BReaction 1
Enzyme 2
CReaction 2
Enzyme 3
DReaction 3
ProductStartingmolecule
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• Catabolic pathways release energy by breaking down complex molecules into simpler compounds
• Anabolic pathways consume energy to build complex molecules from simpler ones
• Bioenergetics is the study of how organisms manage their energy resources
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Forms of Energy
• Energy is the capacity to cause change
• Energy exists in various forms, some of which can perform work
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• Kinetic energy is energy associated with motion– Heat (thermal energy) is kinetic energy associated
with random movement of atoms or molecules
• Potential energy is energy that matter possesses because of its location or structure
– Chemical energy is potential energy available for release in a chemical reaction
• Energy can be converted from one form to another
LE 8-2On the platform,the diver hasmore potentialenergy.
Diving convertspotentialenergy to kinetic energy.
Climbing up convertskinetic energy ofmuscle movement topotential energy.
In the water, the diver has lesspotential energy.
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The First Law of Thermodynamics
• According to the first law of thermodynamics, the energy of the universe is constant
– Energy can be transferred and transformed
– Energy cannot be created or destroyed
• The first law is also called the principle of conservation of energy
LE 8-3
Chemical energy
Heat CO2
First law of thermodynamics Second law of thermodynamics
H2O
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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
LE 8-6a
Reactants
EnergyProducts
Progress of the reaction
Amount ofenergy
released(G < 0)
Free
ene
rgy
Exergonic reaction: energy released
LE 8-6b
ReactantsEnergy
Products
Progress of the reaction
Amount ofenergy
required(G > 0)
Free
ene
rgy
Endergonic reaction: energy required
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The Structure and Hydrolysis of ATP
• ATP (adenosine triphosphate) is the cell’s energy shuttle
• ATP provides energy for cellular functions
LE 8-8
Phosphate groupsRibose
Adenine
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• The bonds between the phosphate groups of ATP’s tail can be broken by hydrolysis
• Energy is released from ATP when the terminal phosphate bond is broken
LE 8-9
Adenosine triphosphate (ATP)
Energy
P P P
PPP i
Adenosine diphosphate (ADP)Inorganic phosphate
H2O
+ +
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• In the cell, the energy from the exergonic reaction of ATP hydrolysis can be used to drive an endergonic reaction
• Overall, the coupled reactions are exergonic
LE 8-10Endergonic reaction: G is positive, reactionis not spontaneous
Exergonic reaction: G is negative, reactionis spontaneous
G = +3.4 kcal/mol
G = –7.3 kcal/mol
G = –3.9 kcal/mol
NH2
NH3Glu Glu
Glutamicacid
Coupled reactions: Overall G is negative;together, reactions are spontaneous
Ammonia Glutamine
ATP H2O ADP P i
+
+ +
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How ATP Performs Work
• ATP drives endergonic reactions by phosphorylation, transferring a phosphate group to some other molecule, such as a reactant
• The recipient molecule is now phosphorylated
• The three types of cellular work (mechanical, transport, and chemical) are powered by the hydrolysis of ATP
LE 8-11
NH2
Glu
P i
P i
P i
P i
Glu NH3
P
P
P
ATPADP
Motor proteinMechanical work: ATP phosphorylates motor proteins
Protein moved
Membraneprotein
Solute
Transport work: ATP phosphorylates transport proteins
Solute transported
Chemical work: ATP phosphorylates key reactants
Reactants: Glutamic acidand ammonia
Product (glutamine)made
+ +
+
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The Regeneration of ATP
• ATP is a renewable resource that is regenerated by addition of a phosphate group to ADP
• The energy to phosphorylate ADP comes from catabolic reactions in the cell
• The chemical potential energy temporarily stored in ATP drives most cellular work
LE 8-12
Pi
ADP
Energy for cellular work(endergonic, energy-consuming processes)
Energy from catabolism(energonic, energy-yielding processes)
ATP
+
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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
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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
G < O
Progress of the reaction
Reactants
C D
A B
Free
ene
rgy
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How Enzymes Lower the EA Barrier
• Enzymes catalyze reactions by lowering the EA barrier
LE 8-15
Course ofreactionwithoutenzyme
EA
without enzyme
G is unaffectedby enzyme
Progress of the reaction
Free
ene
rgy
EA withenzymeis lower
Course ofreactionwith enzyme
Reactants
Products
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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
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Catalysis in the Enzyme’s Active Site
• In an enzymatic reaction, the substrate binds to the active site
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.
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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
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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
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Cofactors
• Cofactors are nonprotein enzyme helpers
• Coenzymes are organic cofactors
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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.
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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
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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
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• 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
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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)