An Introduction to Metabolism - WordPress.com · 11/8/2012 · An Introduction to Metabolism Chapter 8 . What is metabolism? • The sum of chemical reactions within a living organism

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

PowerPoint® Lecture Presentations for

Biology

Eighth Edition

Neil Campbell and Jane Reece

Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp

An Introduction to

Metabolism

Chapter 8

What is metabolism?

• The sum of chemical reactions

within a living organism

• Metabolism is an emergent

property of life that arises from

interactions between molecules

within the cell

• An organism’s metabolism

transforms matter and energy,

subject to the laws of

thermodynamics

C6H12O6 + 6O2

6CO2 + 6H2O

+ energy e-

Overview: The Energy of Life

The living cell is a miniature chemical factory

where thousands of reactions occur

The cell extracts energy and uses energy to

perform work (e.g. breaking chemical bonds, movement)

Some organisms even convert energy to light,

as in bioluminescence


Bioluminescence in deep-sea organisms

Organization of the Chemistry of Life into Metabolic Pathways

• Metabolism arranged into a series of

metabolic pathways beginning with a specific

molecule and ending with a product

• Each step is catalyzed by a specific enzyme


Enzyme 1 Enzyme 2 Enzyme 3

D C B A Reaction 1 Reaction 3 Reaction 2

Starting molecule

Product

The mechanisms that regulate enzymes balance metabolic

supply and demand, adverting deficits or surpluses of

important cellular molecules.

Metabolism manages energy resources of the cell to make

it as efficient as possible

Generalized metabolic pathway

What Physical Principles Underlie Biological Energy Transformations?

Anabolic reactions: complex molecules are made from simple molecules; energy input is required.

Catabolic reactions: complex molecules are broken down to simpler ones and energy is released.

Metabolism = Catabolism and Anabolism

• Catabolic Reactions:

The breakdown of complex organic molecules into simpler molecules

Generally hydrolytic (Water added to break a bond)

exergonic (produce energy)-energy stored in chemical bonds is

released

Cellular respiration, the breakdown of glucose in the presence of

oxygen, is an example of a pathway of catabolism

• Anabolic Reactions:

The synthesis of complex organic molecules from simpler molecules

Generally dehydration synthesis reactions (water released when the

bond is formed)

Endergonic (consume energy)

The synthesis of protein from amino acids is an example of anabolism

• Energy is the capacity to cause change

• Energy exists in various forms.

• Energy can be converted from one form to

another (Examples of energy conversions?)


Metabolism is transfer of energy

Energy Conversions

• All forms of energy can be converted into other forms.

The sun’s energy through solar cells can be

converted directly into electricity.

Green plants convert the sun’s energy

(electromagnetic energy) into starches and

sugars (chemical energy).


All forms of energy can be placed in two

categories:

1) Potential energy is stored energy—as chemical

bonds, concentration gradient, charge imbalance,

etc.

• Chemical potential energy is energy available for release

in a chemical reaction (food is stored chemical energy)

2) Kinetic energy is the energy of movement.

• Heat (thermal energy) is kinetic energy associated with

• random movement of atoms or molecules

Fig. 8-2

Climbing up converts the kinetic

energy of muscle movement

to potential energy.

A diver has less potential

energy in the water

than on the platform.

Diving converts

potential energy to

kinetic energy.

A diver has more potential

energy on the platform

than in the water.

Thermodynamic Systems - An overview

• A system is a group of interacting,

interrelated, or interdependent

elements forming a complex whole.

• Energy transfer is studied in two

types of systems:

– 1. Open systems

– 2. Closed systems (Isolated

systems)

Thermodynamics is the study of energy transformations

The Laws of Energy Transformation

• A closed (isolated) system

isolated from its surroundings

Unable to exchange either energy or matter with its surroundings

• Example: thermos


The Laws of Energy Transformation

open systems

energy and matter transferred between the system and its surroundings.

Example: all organisms are open systems

– They absorb energy (light or chemical energy) in the for of organic molecules and release waste and metabolic products, such as CO2, to the surroundings.


First Law of Thermodynamics: Energy

is neither created nor destroyed.

When energy is converted from one form

to another, the total energy before and

after the conversion is the same.

The first law is also called the principle of conservation

of energy


Second Law of Thermodynamics: When energy is

converted from one form to another, some of that

energy becomes unavailable to do work.

No energy transformation is 100 % efficient.

Usually this energy is lost in the form of HEAT (= random energy of molecular

movement)

Example: only 25% of chemical energy stored in gasoline is transformed in to

motion of the car- 75% is lost as heat!!

Figure 6.2 The Laws of Thermodynamics

The Second Law of Thermodynamics (stated in a different way)

•

According to the second law of thermodynamics:

Every energy transfer or transformation increases

the entropy (disorder or randomness) of the

Universe

THE UNIVERSE SPONTANEOUSLY GOES

TOWARDS “RANDOMNESS”


All living systems obey the laws of thermodynamics

(a) First law of thermodynamics

Energy can be transferred or

transformed but neither created

or destroyed.

(b) Second law of thermodynamics

Every energy transfer or transformation increases the disorder

(entropy) of the universe.

Chemical energy

Heat

CO2

H2O

+

Fig. 8-4

50 µm

As open system, organisms can increase their order

as long as the order of their surroundings decrease.


In any system:

total energy = usable energy + unusable energy

Enthalpy (H) = Free Energy (G) + Entropy (S)

or H = G + TS (T = absolute temperature)

G = H – TS


Change in energy can be measured in

calories or joules.

Change in free energy (ΔG) in a reaction

is the difference in free energy of the

products and the reactants.


ΔG = ΔH – TΔS

If ΔG is negative, free energy is released.

If ΔG is positive, free energy is consumed.

If free energy is not available, the reaction

does not occur.


ΔG = ΔH – TΔS

Magnitude of ΔG depends on:

ΔH—total energy added (ΔH > 0) or

released (ΔH < 0).

ΔS—change in entropy. Large changes in

entropy make ΔG more negative.


If a chemical reaction increases entropy,

the products will be more disordered.

Example: hydrolysis of a protein into its

component amino acids—ΔS is

positive.


Exergonic reactions release free energy

(–ΔG)—catabolism

Endergonic reactions consume free

energy (+ΔG)—anabolism

Figure 6.3 Exergonic and Endergonic Reactions


In principle, chemical reactions can run in

both directions.

Chemical equilibrium ΔG = 0

Forward and reverse reactions are

balanced.

BA

Figure 6.4 Chemical Reactions Run to Equilibrium

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

• Will the following reaction occur

Spontaneously????

• PO42- + glucose glucose-6-phosphate

• To do so, they need to determine energy

changes that occur in chemical reactions


Spontaneous or not Spontaneous

• PO42- + glucose glucose-6-phosphate

Will NOT occur spontaneously!

WHY?

The change in energy between the reactants

(PO42- + glucose) and the products (glucose-6-

phosphate) measured and found that the

products contain more energy!

Figure 6.3 Exergonic and Endergonic Reactions

Only processes with a negative ∆G are

spontaneous (do not require energy input)

• Energy released in spontaneous processes

can be harnessed to perform work


Spontaneous or not Spontaneous

Free Energy, Stability, and Equilibrium

• During a spontaneous change, free energy

decreases 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

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

• 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 stable

• The released free energy can be harnessed to do work

• Less free energy (lower G)

• More stable • Less work capacity

The relationship of free energy to stability, work capacity, and spontaneous change.

Unstable systems (top diagram) are rich in free energy, G. They have tendency to

change spontaneously to a more stable state (bottom), and it is possible to harness this

“downhill” change to perform work.

Free Energy and Metabolism

• The concept of free energy can be applied to

the chemistry of life’s processes


Exergonic and Endergonic Reactions in Metabolism

• An exergonic reaction proceeds with a net

release of free energy and is spontaneous

(Negative ∆G )

• An endergonic reaction absorbs free energy

from its surroundings and is nonspontaneous

(Positive ∆G )


Fig. 8-6 Free energy changes (∆G) in exergonic and endergonic reactions.

Reactants

Energy

Fre

e e

ne

rgy

Products

Amount of energy

released (∆G < 0)

Progress of the reaction

(a) Exergonic reaction: energy released

Products

Reactants

Energy

Fre

e e

ne

rgy

Amount of energy

required

(∆G > 0)

(b) Endergonic reaction: energy required


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 materials

• A defining feature of life is that metabolism is

never at equilibrium

• A catabolic pathway in a cell releases free energy

in a series of reactions

• Closed and open hydroelectric systems can serve

as analogies


Fig. 8-7a

(a)An isolated 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.

∆G < 0 ∆G = 0

Fig. 8-7b

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

∆G < 0

Fig. 8-7c

(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. The product of each reaction Become the reactant for the next, so no reaction reach equilibrium.

∆G < 0

∆G < 0

∆G < 0

Equilibrium and Metabolism

• Reactions in a closed system eventually reach

equilibrium and then do no work.

• Cells and organism are not in equilibrium; they are

open systems experiencing a constant flow of

materials.

An Egyptian Mummy

Cellular work performed by coupling exergonic reactions to endergonic reactions

• A cell does three main kinds of work:

– Chemical

– Transport

– Mechanical

• How do cells get non-spontaneous reactions to occur?

• ……… by energy coupling, the use of an exergonic

process to drive an endergonic one

• Most energy coupling in cells is mediated by ATP


The three

types of

cellular

work:

Mechanical,

Transport

and

Chemical

are powered

by the

hydrolysis of

ATP

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

groups


Fig. 8-8 The structure of adenosine triphosphate (ATP)

Phosphate groups Ribose

Adenine

All three phosphate groups are negatively charged. These like charges are crowed together,

and their repulsion contributes to the instability of this region of the ATP molecule. The

triphosphate tail of ATP is the chemical equivalent of a compressed spring.

• 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

Fig. 8-9 The hydrolysis of ATP

Inorganic phosphate

Energy

Adenosine triphosphate (ATP)

Adenosine diphosphate (ADP)

P P

P P P

P + +

H2O

i

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

reaction of ATP hydrolysis can be used to drive

an endergonic reaction

• Overall, the coupled reactions are exergonic

(spontaneous)


Fig. 8-10

(b) Coupled with ATP hydrolysis, an exergonic reaction

Ammonia displaces the phosphate group, forming glutamine.

(a) Endergonic reaction

(c) Overall free-energy change

P

P

Glu

NH3

NH2

Glu i

Glu ADP +

P

ATP +

+

Glu

ATP phosphorylates glutamic acid, making the amino acid less stable.

Glu

NH3

NH2

Glu +

Glutamic acid

Glutamine Ammonia

∆G = +3.4 kcal/mol

+ 2

1

Fig. 8-11 How ATP drives transport and mechanical work

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

Membrane protein

P i

ADP +

P

Solute Solute transported

P i

Vesicle Cytoskeletal track

Motor protein Protein moved

(a) Transport work: ATP phosphorylates transport proteins

ATP

ATP

The 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 from

catabolic reactions in the cell

• The chemical potential energy temporarily

stored in ATP drives most cellular work


Fig. 8-12 The ATP cycle Energy released by breakdown reactions (catabolism) in the cell is used to phosphorylate ADP, regenerating ATP. Chemical potential energy stored in ATP drives most cellular work.

P i ADP +

Energy from catabolism (exergonic, energy-releasing processes)

Energy for cellular work (endergonic, energy-consuming processes)

ATP + H2O

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


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


Fig. 8-14 Energy profile of an exergonic reaction


Products

Reactants

∆G < O

Transition state

EA

D C

B A

D

D

C

C

B

B

A

A

The reactants must absorb enough

energy from the surroundings to

reach the unstable transition state

where bonds can break.

After bonds have broken,

new bonds form, releasing

energy to the surroundings.

How Enzymes Lower the EA Barrier

• Enzymes catalyze reactions by lowering the EA

barrier of reaction

• An enzyme cannot change the ∆G for a reaction; it

cannot make an endorgonic reaction exergonic

Animation: How Enzymes Work


08_15HowEnzymesWork_A.html


Products

Reactants

∆G is unaffected by enzyme

Course of reaction without enzyme

EA

without

enzyme EA with

enzyme is lower

Course of reaction with enzyme

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 fit is highly specific!

• The active site is the region on the enzyme where the

substrate binds


The enzyme is NOT

changed in the

reaction

Substrate

Active site

Enzyme

Enzyme-substrate complex

(b) When the substrate enters the active site, it induces a change in the shape of the protein. This change allows active site to enfold the substrate and hold it in place

(a) The active site of this enzyme forms a groove on its surface.

Enzymes and substrates fit together like a hand

in a glove

Induced fit of a substrate brings chemical groups of the active

site into positions that enhance their ability to catalyze the

reaction

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


Substrates

Enzyme

Products are released.

Products

Substrates are converted to products.

Active site can lower EA and speed up a reaction.

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

Substrates enter active site; enzyme

changes shape such that its active site

enfolds the substrates (induced fit).

Active site is

available for two new

substrate molecules.

Enzyme-substrate complex

5

3

2

1

6

4

Fig. 8-17 The active site and catalytic cycle of an enzyme

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


Fig. 8-18 Environmental factors affecting enzyme activity

Ra

te o

f re

acti

on

Optimal temperature for enzyme of thermophilic

(heat-tolerant) bacteria

Optimal temperature for typical human enzyme

(a) Optimal temperature for two enzymes

(b) Optimal pH for two enzymes

Rate

of

reacti

on

Optimal pH for pepsin (stomach enzyme)

Optimal pH for trypsin (intestinal enzyme)

Temperature (ºC)

pH

5 4 3 2 1 0 6 7 8 9 10

0 20 40 80 60 100

Cofactors

• Some enzymes need a partner 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


Enzyme Inhibitors

• Enzyme activity needs to be regulated

• 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


(a) Normal binding A substrate can bind normally to the active site of an enzyme

(c) Noncompetitive inhibition binds to the enzyme away from the active site, altering the shape of the enzyme so that even the substrate can bind, the active site function less effective

(b) Competitive inhibition Mimics the substrate, competing for active site

Noncompetitive inhibitor

Active site

Competitive inhibitor

Substrate

Enzyme

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 once

they are made


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

– It may result in either inhibition or stimulation of

an enzyme’s activity


Allosteric Activation and Inhibition

• 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


Fig. 8-20 Allosteric regulation of enzyme activity.

Allosteric enyzme with four subunits

Active site (one of four)

Regulatory site (one of four)

Active form

Activator

Stabilized active form

Oscillation

Non- functional active site

Inhibitor Inactive form Stabilized inactive

form

(a) Allosteric activators and inhibitors

Substrate

Inactive form Stabilized active form

(b) Cooperativity: another type of allosteric activation

Fig. 8-20a

(a) Allosteric activators and inhibitors . In the cell, activators and inhibitors dissociate when at low concentrations. The enzyme can then oscillate again.

Inhibitor Non- functional active site

Stabilized inactive form

Inactive form

Oscillation

Activator

Active form Stabilized active form

Regulatory site (one of four)

Allosteric enzyme with four subunits

Active site (one of four)

• 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


Fig. 8-20b

(b) Cooperativity: another type of allosteric activation The inactive form shown on the left oscillates back and forth with the active form when the active form is not stability by substrate.

Stabilized active form

Substrate

Inactive form

Identification of Allosteric Regulators

• Allosteric regulators are attractive drug

candidates for enzyme regulation

• Inhibition of proteolytic enzymes called

caspases may help management of

inappropriate inflammatory responses


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


Fig. 8-22 Feedback inhibition in isoleucine synthesis.

Intermediate C

Feedback inhibition

Isoleucine used up by cell

Enzyme 1 (threonine deaminase)

End product

(isoleucine)

Enzyme 5

Intermediate D

Intermediate B

Intermediate A

Enzyme 4

Enzyme 2

Enzyme 3

Initial substrate (threonine)

Threonine in active site

Active site available

Active site of enzyme 1 no longer binds threonine; pathway is switched off.

Isoleucine binds to allosteric site

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


Fig. 8-23 Organelle and structural order in metabolism

1 µm

Mitochondria

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. Describe the mechanisms by which enzymes

lower activation energy

7. Describe how allosteric regulators may inhibit

or stimulate the activity of an enzyme


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An Introduction to Metabolism - WordPress.com · 11/8/2012 · An Introduction to Metabolism Chapter 8 . What is metabolism? • The sum of chemical reactions within a living organism