copyright © 2005 pearson education, inc. publishing as benjamin cummings chapter 8: an introduction...

Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings

Chapter 8: An introduction to Metabolism


Is a living organism anopen or closed system?Explain your answer.

Start Your Engines


Metabolism

• Metabolism in the living cell

– Miniature factory where thousands of reactions or energy conversions occur

– Energy

• Free energy

• Energy in Biological systems

• ATP

– Enzymes

• Function

• Regulation


Starter.

Explain the concept ofenergy coupling in the of biological system. (hint: think ATP)


Metabolism

• What is Metabolism

– The totality of an organisms chemical reactions.


Metabolism

• Metabolism transforms matter and energy, subject to the laws of thermodynamics

1. Energy can be transferred andtransformed but NOT destroyed

2. Every energy transformation Increases the entropy in the

universe.

Energy Conversion is not 100%


Metabolic Pathways Metabolism is Controlled

– Metabolism occurs in pathways sometimes with many steps.

– Begins w/ specific molecule, ends w/ product

– Each step catalyzed by specific enzyme

Enzyme 1 Enzyme 2 Enzyme 3

A B C D

Reaction 1 Reaction 2 Reaction 3

Startingmolecule

Product


Metabolism

• Catabolic pathways

– Complex molecules simpler compounds

– Release energy Proteins

Amino Acids


Metabolism

• Anabolic pathways

– Build complicated molecules from simpler ones

– Consume energy


Energy

• Energy can be converted from one form to another On the platform, a diver

has more potential energy.Diving converts potentialenergy to kinetic energy.

Climbing up converts kineticenergy of muscle movement to potential energy.

In the water, a diver has less potential energy.

Figure 8.2

Kinetic Potential Chemical Thermal


Energy in a Biological System

• Energy conversion

Chemicalenergy


The Second Law of Thermodynamics

• Spontaneous changes increase the entropy, or disorder, of the universe

Heatco2

H2O

+

Energy Conversion is not 100%


Energy

• Living systems

– Increase entropy of the universe

– Use energy to maintain order50µm

Figure 8.4


Free-Energy Change, G

• Determines if reaction occurs spontaneously


Energy

• Change in free energy, ∆G during a biological process

– Related directly to the enthalpy (total energy of a system ∆H) change and the change in entropy

∆G = ∆H – T∆S

∆Free energy= ∆(Enthalpy) – T∆(Entropy)Negative ∆G= SpontaneousPositive ∆G = Requires energy


Exergonic reaction

• Net release of free E, spontaneous

Figure 8.6

Reactants

Products

Energy

Progress of the reaction

Amount ofenergyreleased (∆G <0)

Fre

e e

ner

gy

(a) Exergonic reaction: energy released


Endergonic reaction

• Absorbs free E from surroundings, nonspontaneous

Figure 8.6

Energy

Products

Amount ofenergyreleased (∆G>0)

Reactants


Fre

e e

ner

gy

(b) Endergonic reaction: energy required


Energy in a Biological Systems

• Maximum stability system at equilibrium

Chemical reaction. In a cell, a sugar molecule is broken down into simpler molecules.

.

Diffusion. Molecules in a drop of dye diffuse until they are randomly dispersed.

Gravitational motion. Objectsmove spontaneously from ahigher altitude to a lower one.

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

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

In a spontaneously 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

(a) (b) (c)

Figure 8.5


Metabolic pathways as systems: Closed System

• Reactions in a closed system eventually reach equilibrium

∆G < 0 ∆G = 0


Open System

• Cells constant flow of materials in and out, do not reach equilibrium

∆G < 0


Multi-Step Open System

• Analogy for cellular respiration

∆G < 0

∆G < 0

∆G < 0

Holy Exergonic Reactions

Batman!


ATP Cellular Energy Currency

• (adenosine triphosphate)

– Cell’s Energy shuttle. ATP powers cellular work by coupling exergonic reactions to endergonic reactions

Figure 8.8

O O O O CH2

H

OH OH

H

N

H H

O

NC

HC

N CC

N

NH2Adenine

RibosePhosphate groups

O

O O

O

O

O

-

- - -

CH


ATP

• E released from ATP when terminal phosphate bond is broken (hydrolysis)

Figure 8.9

P

Adenosine triphosphate (ATP)

H2O

+ Energy

Inorganic phosphate Adenosine diphosphate (ADP)

PP

P PP i


ATP Must look at total ∆G

• ATP hydrolysis coupled to other reactionsEndergonic reaction: ∆G is positive, reaction is not spontaneous

∆G = +3.4 kcal/mol

Glu Glu

∆G = - 7.3 kcal/mol

ATP H2O+

+ NH3

ADP +

NH2

Glutamicacid

Ammonia Glutamine

Exergonic reaction: ∆ G is negative, reaction is spontaneous

P

Coupled reactions: Overall ∆G is negative; together, reactions are spontaneous ∆G = –3.9 kcal/mol


Cellular work powered by hydrolysis of ATP

(c) Chemical work: ATP phosphorylates key reactants

P

Membraneprotein

Motor protein

P i

Protein moved

(a) Mechanical work: ATP phosphorylates motor proteins

ATP

(b) Transport work: ATP phosphorylates transport proteins

Solute

P P i

transportedSolute

GluGlu

NH3

NH2

P i

P i

+ +

Reactants: Glutamic acid and ammonia

Product (glutamine)made

ADP+

P


Regeneration of ATP Energy from Food!!

• Catabolic pathways: ATP from ADP and phosphate (ATP Synthesis)

ATP synthesis from ADP + P i requires energy

ATP

ADP + P i

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

Energy from catabolism(exergonic, energy yieldingprocesses)

ATP hydrolysis to ADP + P i yields energy

Figure 8.12


Enzymes

• Proteins, speed up metabolic reactions by lowering E barriers

• Catalyst: speeds up a reaction w/o being consumed by the reaction

Proximity


Enzymes

• Substrate

– Reactant an enzyme acts on

• Enzyme

– Binds to substrate, forming enzyme-substrate complex

Enzyme

Complex

Substrate


Enzymes Lower the EA Barrier

• Activation energy, EA Initial amount of E needed to start a chemical reaction. Often in the form of heat


Products

Course of reaction without enzyme

Reactants

Course of reaction with enzyme

EA

withoutenzyme EA with

enzymeis lower

∆G is unaffected by enzymeF

ree

ener

gy

Figure 8.15

Even w/-∆G reactionmay be tooslow biologically


How Enzymes Work

• Active site

– Region on enzyme where the substrate binds

Figure 8.16

Substate

Active site

Enzyme

(a)


• Induced fit of substrate

– substrate in positions that enhance catalysis

Figure 8.16 (b)

Enzyme- substratecomplex

Can be multipleactive sites


Catalytic cycle of an enzyme

Conformational change

Substrates

Products

Enzyme

Enzyme-substratecomplex

1 Substrates enter active site; enzymechanges shape so its active siteembraces the substrates (induced fit).

2 Substrates held inactive site by weakinteractions, such ashydrogen bonds andionic bonds.

3 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.

4 Substrates are Converted intoProducts.

5 Products areReleased.

1 6 Active siteIs available fortwo new substrateMole.

Figure 8.17


Enzymes

• Enzymes have optimal conditions in which they function

Figure 8.18

Optimal temperature for enzyme of thermophilic

Rat

e o

f re

actio

n

0 20 40 80 100Temperature (Cº)

(a) Optimal temperature for two enzymes

Optimal temperature fortypical human enzyme

(heat-tolerant) bacteriaTemp

pH


Enzymes

• Cofactors

– Nonprotein enzyme helper

Cu+, Mg2+, Mn2+

• Coenzymes

– Organic cofactors

NAD, FAD, vitamins


Enzyme Regulation

• Regulation of enzyme activity controls metabolism

• Cell’s metabolic pathways tightly regulated


Enzyme Regulation: Competitive inhibitors

• Bind to active site, compete w/ substrate

Figure 8.19 (b) Competitive inhibition

A competitiveinhibitor mimics thesubstrate, competing

for the active site.

Competitiveinhibitor

A substrate canbind normally to the

active site of anenzyme.

Substrate

Active site

Enzyme

(a) Normal binding


Enzyme regulation: Noncompetitive inhibitors

• Bind to another part of enzyme, changing function

Figure 8.19

A noncompetitiveinhibitor binds to the

enzyme away fromthe active site, altering

the conformation ofthe enzyme so that its

active site no longerfunctions.

Noncompetitive inhibitor

(c) Noncompetitive inhibition


Enzyme Regulation: Allosteric

• Protein’s function at one site is affected by binding of a regulatory molecule at another site

Stabilized inactiveform

Allosteric activaterstabilizes active fromAllosteric enyzme

with four subunitsActive site

(one of four)

Regulatorysite (oneof four)

Active formActivator

Stabilized active form

Allosteric inactivaterstabilizes inactive form

InhibitorInactive form

Non-functionalactivesite

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

Oscillation

Figure 8.20


Enzyme regulation: Cooperativity

• Cooperativity; allosteric regulation that amplifies enzyme activity

Figure 8.20

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

Substrate

Inactive form Stabilized active form

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


Enzyme Regulation: Feedback Inhibition

• End product of metabolic pathway shuts down pathway Active site

available

Isoleucineused up bycell

Feedbackinhibition

Isoleucine binds to allosteric site

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

Initial substrate(threonine)

Threoninein active site

Enzyme 1(threoninedeaminase)

Intermediate A

Intermediate B

Intermediate C

Intermediate D

Enzyme 2

Enzyme 3

Enzyme 4

Enzyme 5

End product(isoleucine)

Figure 8.21

copyright © 2005 pearson education, inc. publishing as benjamin cummings chapter 8: an introduction...

Documents

energy free energy energy

potential energy

energy products

energy conversions

energy transformation

pearson education

free energy lower g

free energy higher g