An Introduction to Metabolism - s3.amazonaws.com · transformation increases the disorder (entropy) of the universe. For example, disorder is added to the cheetah’s surroundings

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Chapter 8Chapter 8

An Introduction to Metabolism

Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Lectures by Chris Romero, edited by Erin Barley, Joan Sharp, and Janette Lewis

PowerPoint Lectures for Biology, Eighth Edition

Overview: The Energy of Life

• The living cell is a miniature chemical factory where thousands of reactions occur

• The cell extracts energy and applies energy to perform work

• Some organisms even convert energy to light,Some organisms even convert energy to light, as in bioluminescence


Bioluminescent Fungi An Introduction to Metabolism

• Topics1. Metabolism and the transfer of energy2. Free-energy and spontaneous reactions3. ATP4. Enzymes

Concept 8.1: An organism’s metabolism transforms matter and energy, subject to the laws of thermodynamics

• Metabolism is the totality of an organism’s chemical reactions

• “Metabolism is an emergent property of life that arises from interactions between molecules within the cell”– Metabolism is a highly complex series of chemical

reactions catalyzed by many, highly complex enzymes which would all have had to evolve at the same time through random mutations in DNA.


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• Two general types metabolic pathways:Two general types metabolic pathways:

catabolic and anabolic pathways


Enzyme 1 Enzyme 2 Enzyme 3DCBA

Reaction 1 Reaction 3Reaction 2Startingmolecule

Product

2

– Catabolic pathways • release energy by breaking down complex

molecules into simpler compounds• Cellular respiration, the breakdown of

glucose in the presence of oxygen, is an

Metabolic Pathways

example of a pathway of catabolism


– Anabolic pathways • consume energy to build complex molecules

from simpler ones• The synthesis of protein from amino acids is

an example of anabolism

Metabolic Pathways

– Bioenergetics is the study of how organisms manage their energy resources


Metabolic Pathways

• Forms of Energy– Energy is the capacity to cause change– Energy exists in various forms, some of

which can perform workEnergy can be converted from one form to– Energy can be converted from one form to another.

– Forms of energy include: kinetic, potential, thermal, and chemical energy.


• Kinetic energy is energy associated with motion

• Heat (thermal energy) is kinetic energy associated with random movement of atoms or molecules

Forms of Energy

• 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

Animation: Energy ConceptsAnimation: Energy Concepts


Energy can be converted from one form to anotherOn the platform, a diverhas more potential energy.

Diving converts potentialenergy to kinetic energy.

Climbing up converts kinetic energy of muscle movement to potential energy.

In the water, a diver hasless potential energy.

Metabolism: The Laws of Energy Transformation

• The laws of energy transformation– Thermodynamics is the study of energy

transformations• A closed system, such as that approximated

by liquid in a thermos, is isolated from its y qsurroundings

• In an open system, energy and matter can be transferred between the system and its surroundings. Organisms are open systems.

– Two laws of thermodynamics, 1st & 2nd


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Thermodynamics

1. The first law of thermodynamics, • Energy can be transferred and transformed,

but it cannot be created or destroyed• The first law is also called the principle of

conservation of energy• The energy of the universe is constant:


The First Law of Thermodynamics

First law of thermodynamics:Energy can be transferred or transformed but neither ChemicalChemical

H2O

created nor destroyed. For example, the chemical (potential) energy in food will be converted to the kinetic energy of the cheetah’s movement

energyenergy

Thermodynamics

2. Second law of thermodynamics:

• Every energy transfer or transformation increases the entropy (disorder) of the universe

• During every energy transfer or transformation, some energy is unusable, and is often lost as heat


H2O

co2

+

The Second Law of Thermodynamics

Second law of thermodynamics: Every energy transfer or transformation increases the disorder (entropy) of the universe. For example, disorder is added to the cheetah’s surroundings in the form of heat and the small molecules that are the by-products of metabolism.

Thermodynamics

• Biological Order and Disorder– Cells create ordered structures from less

ordered materials using energy AND the intelligent instructions found in DNA

– Organisms also replace ordered forms of matter and energy with less ordered forms

– Energy flows into an ecosystem in the form of light, is converted to chemical energy using complex machinery of photosynthesis, and exits in the form of heat after organisms convert energy to other forms in respiration.


Thermodynamics

• The input of energy alone is insufficient to explain how the order found in this plant root evolved by natural processes.

50 µm

4

Two Types of Causes

Intelligent Processes

Only intelligence + energycan decrease entropy on a

l l

Natural Processes

Increase entropy

large scale

Thermodynamics and Biological Order

• DNA contains staggering amounts of information. – It’s not surprising that living things can then

become more orderly with the input of energy, using the instruction found in DNA.

– The 2nd Law still applies – they lose energy in the process of growth, and the food is not processed at 100% efficiency.

Thermodynamics and Biological Order

• The Real Question: “How did life arise from nonliving chemicals, without intelligent intervention, when nonliving chemicals are susceptible to the Second Law of thermodynamics?” – We’re not talking about what something can do

once it’s alive – it already has it’s DNA. – How did life arise in the first place through

natural processes? – How can the origin of DNA, be explained by

natural processes?

Quote by Richard Dawkins, The Blind Watchmaker

• “Biology is the study of complicated things that give the appearance of having been designed for a purpose ” pg 1 “T l t D kipurpose. pg. 1

• He also acknowledges “the intricate architecture and precision engineering” of human life.

• “Two pages later, Dawkins flatly denies that life was designed. He refuses to allow observation to interfere with his conclusion.”

– Geisler, I Don’t Have Enough Faith to be an Atheist, pg 119

• How would you respond to this claim from your book?– “The evolution of more complex organisms

does not violate the second law of thermodynamics. Entropy (disorder) may

Quote from Book

y py ( ) ydecrease in an organism, but the universe’s total entropy increases.”


Review Questions

• Which of the following statements correctly describe(s) catabolic pathways?A. They do not depend on enzymes.B. They consume energy to build up polymers

from monomers.C. They release energy as they degrade

polymers to monomers.D. They lead to the synthesis of catabolic

compounds.E. Both A and B


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Review Questions

• Whenever energy is transformed, there is always an increase in theA. free energy of the systemB. free energy of the universeC entropy of the systemC. entropy of the systemD. entropy of the universeE. enthalpy of the universe


• The first cell arose from random natural processes without intelligence acting on the chemicals of the early earth: This statementA. is consistent with the second law of

thermodynamics

What answer would your textbook expect?

B. requires that the entropy of the chemicals decreased

C. provides scientific support for those who believe that evolution could not possible be true because it violates the 2nd law.

• This question came with the test-bank for the 7th Edition.


Concept 8.2: The free-energy change of a reaction tells us whether or not the reaction occurs spontaneously

• Biologists want to know which reactions occur spontaneously and which require input of energy

• To do so, they need to determine energy changes that occur in chemical reactions


Free-Energy Change, ΔG

• Gibs free-energy change, ΔG – A living system’s free energy is energy that

is available do work when temperature and pressure are uniform, as in a living cell

– defined by J. Willard Gibbs, 1878y ,


• Gibbs free-energy change– The change in free energy (∆G) during a

process is related to the change in enthalpy, or change in total energy (∆H), change in entropy (∆S), and temperature in Kelvin (T):


∆G = ∆H – T∆S• Only processes with a negative ∆G are

spontaneous• Spontaneous processes can be harnessed to

perform workCopyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

• When ΔG is negative it means the energy is leaving the system. When ΔG is positive it means energy is entering the system

• An increase in temperature increases entropy (causes more disorder)


( )

∆G = ∆H – T∆S

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Free Energy

• Free energy, stability and equilibruim– Free energy is a measure of a system’s

instability, its tendency to change to a more stable state

– During a spontaneous change, free energy d d h bili fdecreases and the stability of a system increases

– Equilibrium is a state of maximum stability– A process is spontaneous and can perform

work only when it is moving toward equilibrium


Fig. 8-5

• More free energy (higher G)• Less stable• Greater work capacity

In a spontaneous change• The free energy of the systemdecreases (∆G < 0)

• The system becomes moret bl

(a) Gravitational motion (b) Diffusion (c) Chemical reaction

stable• The released free energy can

be harnessed to do work

• Less free energy (lower G)• More stable• Less work capacity

At equilibrium, systems can do no work. As Free energy is released, systems become more stable.

• More free energy• Less stable• Greater work capacity

In a spontaneously change

Chemical reaction.

.

Diffusion. Gravitational motion.

g• The free energy of the

system decreases (∆G<0)

• The system becomes more stable

• The released free energy can be harnessed to do work

(a) (b) (c)

Fig. 8-5a

• More free energy (higher G)• Less stable• Greater work capacity

In a spontaneous change• The free energy of the system

decreases (∆G < 0)• The system becomes more

• Less free energy (lower G)• More stable• Less work capacity

ystable

• The released free energy canbe harnessed to do work

Free Energy

• Free energy and metabolism– An exergonic reaction

• proceeds with a net release of free energy • energy exits the system = -∆G • is spontaneousp

– An endergonic reaction • absorbs free energy from its surroundings • energy enters the system = +∆G • is nonspontaneous


rgy

Amount ofenergy

released(∆G < 0)

Reactants

Free Energy Change in an Exergonic Reaction

Energy

(a) Exergonic reaction: energy released

Progress of the reaction

Free

ene

r

Products

( )

7

rgy

Products

Amount ofenergy

required(∆G > 0)

Free Energy Change in an Endergonic Reaction

Energy

(b) Endergonic reaction: energy required


Free

ene

r (∆G > 0)

Reactants

Equilibrium and Metabolism

• Equilibrium and metabolism– Reactions in a closed system eventually reach

equilibrium and then do no work– Cells are not in equilibrium; they are open

systems experiencing a constant flow of y p gmaterials

– A catabolic pathway in a cell releases free energy in a series of reactions

– Closed and open hydroelectric systems can serve as analogies



• Reactions in a closed system eventually reach equilibrium and then can do no work.

∆G < 0 ∆G = 0

(a) A closed hydroelectric system. Water flowing downhill turns a turbine that drives a generator providing electricity to a light bulb, but only until the system reaches equilibrium.

• An open system– Cells experience a constant flow of materials

in and out, preventing metabolic pathways from reaching equilibrium


(b) An open hydroelectric system. Flowing water keeps driving the generator because intake and outflow of water keep the system from reaching equlibrium.

∆G < 0

• An analogy for cellular respiration

∆G < 0∆G < 0

∆G < 0


(c) A multistep open hydroelectric system. Cellular respiration is analogous to this system: Glucose is broken down in a series of exergonic reactions that power the work of the cell.

Review Questions

• What is the change in free energy of a system at chemical equilibrium?A. slightly increasingB. greatly increasingC slightly decreasingC. slightly decreasingD. greatly decreasingE. no net change

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Remember: ∆G = ∆H - T∆S• When glucose monomers are joined together

by glycosidic linkages to form a cellulose polymer, the changes in free energy, enthalpy, and entropy are as follows:A. +∆G, +∆H, +∆SB. +∆G, +∆H, -∆SC. +∆G, -∆H, -∆SD. -∆G, +∆H, +∆SE. -∆G, -∆H, -∆S

• Cellular respirations uses glucose, which has a high level of free energy, and releases CO2 and water which have low levels of free energy. Is respiration spontaneous?A. yes

Review Questions

yB. no

• Is cellular respiration exergonic or endergonic?

– Exergonic– Endergonic

Review Questions Concept 8.3: ATP powers cellular work by coupling exergonic reactions to endergonic reactions

• A cell does three main kinds of work:1. Chemical2. Transport3 Mechanical3. Mechanical

• To do work, cells manage energy resources by energy coupling, the use of an exergonicprocess to drive an endergonic one– Most energy coupling in cells is mediated by

ATPCopyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Energy Coupling by ATP Powers Cellular Work

• The Structure and Hydrolysis of ATP– ATP (adenosine triphosphate) is the cell’s

energy shuttle– ATP is composed of ribose (a sugar), adenine

(a nitrogenous base), and three phosphate

Phosphate groups Ribose

Adenine

( g ), p pgroups


Stick Model of ATP

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Space Filling Model of ATP

• ATP Hydrolysis– 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

The Structure and Hydrolysis of ATP

p p• Phosphates have a negative charge. • It takes energy to push them together when

they bond. • This energy is released (like a spring) when a

phosphate is broken off.Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Adenosine triphosphate (ATP)

P P P

The Hydrolysis of ATP Releases Energy

Inorganic phosphate

Energy

Adenosine diphosphate (ADP)

P PP ++

H2O

i

How ATP Performs Work

• How ATP performs work– The three types of cellular work (mechanical,

transport, and chemical) are powered by the hydrolysis of ATP

– In the cell, the energy from the exergonic , gy greaction of ATP hydrolysis can be used to drive an endergonic reaction

– Overall, the coupled reactions are exergonic


– ATP drives endergonic reactions by phosphorylation, transferring a phosphate group to some other molecule, such as a reactant

– The recipient molecule is now

How ATP Performs Work

phosphorylated. • The phosphorylated molecule is unstable and

contains more free energy.


(a) Endergonic reaction

NH

GluADP+

PATP+Glu

GluNH3

NH2

Glu+

Glutamicacid

GlutamineAmmonia

∆G = +3.4 kcal/mol

ATP phosphorylatesglutamic acid,making the acid less stable.

1

(b) Coupled with ATP hydrolysis, an exergonic reaction

(c) Overall free-energy change

PP

GluNH3

NH2

Glu i+ +Ammonia displacesthe phosphate group,forming glutamine.

2

10

Membrane protein

ADP+

P

Solute Solute transported

P i

(a) Transport work: ATP phosphorylatestransport proteins

ATP

(b) Mechanical work: ATP binds noncovalently to motor proteins, then is hydrolyzed

P iVesicle Cytoskeletal track

Motor protein Protein moved

ATP

The Regeneration of ATP

• Regeneration of ATP – ATP is a renewable resource that is

regenerated by addition of a phosphate group to adenosine diphosphate (ADP)

– The energy to phosphorylate ADP comes gy p p yfrom catabolic reactions in the cell (require energy)

– The chemical potential energy temporarily stored in ATP drives most cellular work


ATP + H2O

The Regeneration of ATP

P iADP +

Energy fromcatabolism (exergonic,energy-releasingprocesses)

Energy for cellularwork (endergonic,energy-consumingprocesses)

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 proteiny y p• Hydrolysis of sucrose by the enzyme sucrase

is an example of an enzyme-catalyzed reaction


Sucrose (C12H22O11)

Example of an enzyme-catalyzed reaction: the hydrolysis of sucrose by the enzyme sucrase .

Glucose (C6H12O6) Fructose (C6H12O6)

Sucrase

Enzymes Lower Activation Energy Barrier

• 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 gyactivation, or activation energy (EA)

– Activation energy is often supplied in the form of heat from the surroundings


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Transition state

EA

DC

BA

BA

Energy Profile of an Exergonic Reaction


Products

Reactants

∆G < OD

D

C

C

BA

Enzymes Lower the EA Barrier

• Enzymes Lower the EA Barrier– Enzymes do not affect the change in free

energy (∆G); instead, they hasten reactions that would occur eventually

Animation: How Enzymes WorkAnimation: How Enzymes Work


Reactants

Course ofreactionwithoutenzyme

EAwithoutenzyme EA with

enzymeis lower

Enzymes Lower the EA Barrier


Products

∆G is unaffectedby enzyme

Course ofreactionwith enzyme

Substrate Specificity of Enzymes

• How enzymes work– The reactant that an enzyme acts on is called

the enzyme’s substrate – The enzyme binds to its substrate, forming an

enzyme-substrate complexy p– 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


Substrate

Active site

Induced fit between an enzyme and its substrate

Enzyme Enzyme-substratecomplex

(b)(a)

How Enzymes Work

– 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 bondsStraining substrate bonds• Providing a favorable microenvironment • Covalently bonding to the substrate (briefly)


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Substrates

Active site can lower EAand speed up a reaction.

Substrates held in active site by weak interactions, such as hydrogen bonds andionic bonds.

Substrates enter active site; enzyme changes shape such that its active siteenfolds the substrates (induced fit).

Enzyme-substratecomplex 3

2

1

The Catalytic Cycle of an Enzyme

Enzyme

Products arereleased.

Products

Substrates areconverted to products.

p pActivesite is

availablefor two new

substratemolecules.

5

6

4

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

enzymeenzyme


• Effect of temperature on an enzyme– Each enzyme has an optimal temperature in

which it can function– Temp. too low, not enough KE to bring

substrate in contact with active site.


– Temp. too high, protein will denature as bonds are broken that hold it in its 3D shape

– Optimal temp for most enzymes is 35-40 °C


• Effect of pH on enzyme activity– Each enzyme has an optimal pH in which it

can function– The enzyme will begin to denature at extreme

pH’s outside of its optimal range


p p g• The high concentration of H+ in an acid or

the high concentration of OH- in a base interfere with hydrogen bonding in the protein.

Effects of Temperature on Enzyme Activity

Optimal temperature for enzyme of thermophilic

f rea

ctio

n

Optimal temperature fortypical human enzyme

(heat-tolerant) bacteria

Rat

e o

0 20 40 80 100Temperature (Cº)

(a) Optimal temperature for two enzymes

60

te o

f rea

ctio

n

Optimal pH for pepsin (stomach enzyme)

Optimal pHfor trypsin(intestinal

enzyme)

Effects of pH on Enzyme Activity

Rat

(b) Optimal pH for two enzymes10 2 3 4 5 6 7 8 9

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Chemicals that Effect Enzyme Activity

• Cofactors increase enzyme activity– Cofactors are nonprotein enzyme helpers– Cofactors may be inorganic (such as a metal

in ionic form) or organic molecules– An organic cofactor is called a coenzymeAn organic cofactor is called a coenzyme– Coenzymes include vitamins


• Chemicals that decrease enzyme activity– Competitive inhibitors bind to the active

site of an enzyme, competing with the substrate

– Noncompetitive inhibitors bind to another

Chemicals that Effect Enzyme Activity

ppart 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


Active siteCompetitive inhibitor

Substrate

Competitive and Noncompetitive Inhibition

(a) Normal binding (c) Noncompetitiveinhibition

(b) Competitive inhibition

Noncompetitive inhibitor

Enzyme

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 y ggenes that encode specific enzymes or by regulating the activity of enzymes


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

– Most allosterically regulated enzymes are made from polypeptide subunits

– Each enzyme has active and inactive forms


Allosteric Regulation

– 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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Fig. 8-20Allosteric enyzmewith four subunits

Active site(one of four)

Regulatorysite (oneof four)

Active formActivator

Stabilized active form

Oscillation

Non-functionalactivesite

InhibitorInactive form Stabilized inactiveform

(a) Allosteric activators and inhibitors

Substrate

Inactive form Stabilized activeform

(b) Cooperativity: another type of allosteric activation

Fig. 8-20a

Oscillation

ActivatorActive form Stabilized active form

Regulatorysite (oneof four)

Allosteric enzymewith four subunits

Active site(one of four)

(a) Allosteric activators and inhibitors

InhibitorNon-functionalactivesite

Stabilized inactiveform

Inactive form

• Cooperativity – Cooperativity is a form of allosteric

regulation that can amplify enzyme activity– In cooperativity, binding by a substrate to

one active site stabilizes favorable

Allosteric Regulation

conformational changes at all other subunits


Substrate

Allosteric Regulation of Enzyme Activity

(b) Cooperativity: another type of allosteric activation

Stabilized activeform

Inactive form

Allosteric Regulators

• Identification of allosteric regulators– Allosteric regulators are attractive drug

candidates for enzyme regulation– Inhibition of proteolytic enzymes called

caspases may help management ofcaspases may help management of inappropriate inflammatory responses


SH

Substrate

Active form canbind substrate

SH

Activesite

Caspase 1

Known active form

EXPERIMENT

Hypothesis: allostericinhibitor locks enzymein inactive form

S–SSH

Known inactive form

Allostericbinding site

Allostericinhibitor

15

Caspase 1

RESULTS

Active formInhibitor

Allostericallyinhibited form

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 neededp


Feedback inhibition

Active siteavailable

Isoleucine used up by cell

Feedbackinhibition

Active site of enzyme 1 no longer binds

Initial substrate (threonine)

Threonine in active site

Enzyme 1 (threonine deaminase)

Intermediate AEnzyme 2

Isoleucine binds to allosteric site

longer binds threonine;pathway is switched off

Intermediate B

Intermediate C

Intermediate D

Enzyme 3

Enzyme 4

Enzyme 5

End product (isoleucine)

Fig. 8-22

Feedbackinhibition

Isoleucineused up bycell

Enzyme 1(threoninedeaminase)

Intermediate B

Intermediate A

Enzyme 2

Initial substrate(threonine)

Threoninein active site

Active siteavailable

Active site ofenzyme 1 nolonger binds

Intermediate C

End product(isoleucine)

Enzyme 5

Intermediate D

Intermediate B

Enzyme 4

Enzyme 3

gthreonine;pathway isswitched off.

Isoleucinebinds toallostericsite

Specific Localization of Enzymes Within the Cell

• Location of enzymes – Structures within the cell help bring order to

metabolic pathways– Some enzymes act as structural components

of membranesof membranes– In eukaryotic cells, some enzymes reside in

specific organelles; for example, enzymes for cellular respiration are located in mitochondria


Fig. 8-23

Mitochondria

1 µm

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You should now be able to:

1. Distinguish between the following pairs of terms: catabolic and anabolic pathways; kinetic and potential energy; open and closed systems; exergonic and endergonic reactions

2. In your own words, explain the second law of thermodynamics and explain why it is not violated by living organisms

3. Explain in general terms how cells obtain the energy to do cellular work


4. Explain how ATP performs cellular work 5. Explain why an investment of activation

energy is necessary to initiate a spontaneous reaction

6 D ib th h i b hi h

You should now be able to:

6. Describe the mechanisms by which enzymes lower activation energy

7. Describe how allosteric regulators may inhibit or stimulate the activity of an enzyme


Documents

An Introduction to Metabolism - s3.amazonaws.com · transformation increases the disorder (entropy) of the universe. For example, disorder is added to the cheetah’s surroundings