Figure 8-01

This new material we begin today will be on exam #2

Material for exam #1 (March 4) will include these textbook chapters:

Chapter 3-water

Chapter 4-Carbon and the Molecular Diversity of Life (especially functional groups)

Chapter 6-Cell Structure and Function

Chapter 7-Cell Membranes

An Introduction to Metabolism

I. Metabolism, Energy and Life• The chemistry of life is organized into metabolic pathways• Organisms transform energy• The energy transformations of life are subject to two laws of

thermodynamics• Organisms live at the expense of free energy• ATP powers cellular work by coupling exergonic to endergonic

reactionsII. Enzymes• Enzymes speed up metabolic reactions by lowering energy barriers• Enzymes are substrate-specific• The active site is an enzyme’s catalytic centerIII. The Control of Metabolism• Metabolic control often demands allosteric regulation• The location of enzymes within a cell helps to order metabolism

Cell Energetics

• Energy definition-capacity to do work. In terms of cell, what are some types of work that have to be done to stay alive?

Figure 6.2x1 Kinetic and potential energy: dam

Important forms of kinetic and potential

energy for living organisms

• Kinetic-sunlight; heat

• Potential-chemical bond energy (glucose, ATP, etc.)

Cell Energetics are Governed by the Laws of Thermodynamics

• First Law of Thermodynamics (law of Conservation of Energy)

• Energy cannot be created or destroyed but it can be changed in form.

• Energy transformation is permissible (life depends on this happening)-sunlightchemical

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.

Second Law of Thermodynamics

• All matter tends to spontaneously move to the greatest possible state of stability (bonding)

• All matter tends to spontaneously move from areas of higher concentration to lower concentration (diffusion)

• All matter tends to spontaneously move from states of higher free energy (less stable, more concentrated) to states of lower free energy (more stable, less concentrated)

Entropy-Another way to look at the 2nd law of Thermodynamics

• We’ve defined the 2nd law previously in terms of stability and free energy.

• Another way is to understand the 2nd Law is to use the concept of entropy.

• Entropy is the measure of the disorganization of a system

• All systems spontaneously assume the state of greatest entropy.

Cells, entropy, and the 2nd Law of Thermodynamics

• Cells are very organized (low entropy)• How can a cell exist in the face of the 2nd Law (maintain

organization)? Expend energy. • It’s work to stay alive!• The key is that the cell decreases its entropy at the

expense of increasing the entropy of its surroundings. • Cells take ordered (high energy molecules from the

environment and return unordered waste products). • The cell is an open system (can exchange energy with

its environment). • Can a closed system maintain a state of low entropy?

LE 8-3

Chemical energy

Heat CO2

First law of thermodynamics Second law of thermodynamics

H2O

What does the 2nd Law of Thermodynamics say about Life?

• Life is improbable.• Life cannot violate the principle that entropy increases.• Living things live at the expense of their environment

(living things are able to maintain a state of decreased entropy because the entropy of the entire universe (system + surroundings) is increasing

• Life can only exist if energy is constantly being expended.

What form of energy does the cell use to maintain its organization?

• ATP

• ATP cycle

LE 8-8

Phosphate groups

Ribose

Adenine

LE 8-9

Adenosine triphosphate (ATP)

Energy

P P P

PPP i

Adenosine diphosphate (ADP)Inorganic phosphate

H2O

+ +

ATP hydrolysis “releases” energy so that cellular work can be done

• bond breaking versus bond formation

Why does ATP hydrolysis “release” energy?

ATP and cellular work

• How does ATP hydrolysis power cellular work?

• Phosphorylation and dephosphorylation of proteins

LE 8-11

NH2

Glu

P i

P i

P i

P i

Glu NH3

P

P

P

ATPADP

Motor protein

Mechanical 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

+ +

+

How is ATP produced?

• Cellular respiration (cash versus check analogy)

• Difference in autotrophs and heterotrophs

LE 8-UN141

Enzyme 1

A B

Reaction 1

Enzyme 2

C

Reaction 2

Enzyme 3

D

Reaction 3

ProductStarting

molecule

Metabolism and Spontaneous reactions

• Previously stated that catabolic reactions were spontaneous and anabolic were not spontaneous.

Metabolism

• Cell respiration is one example of a metabolic pathway. The chemistry of life is organized into metabolic pathways (complex and regulated by enzymes). (street analogy).

• 2 types of metabolic pathways• a. catabolic-degradative, energy releasing

(downhill), oxidative, spontaneous• b. anabolic-synthetic, energy requiring (up hill),

reduction, not spontaneous

Figure 6.1  The complexity of metabolism

Spontaneous reactions

• What are they?

• They happen on their own without an input of energy

• They are a result of the 2nd law of Thermodynamics

LE 8-5

Gravitational motion Diffusion Chemical reaction

What determines spontaneity of a chemical reaction?

• A +B C+D (substrate products)• Spontaneous-decrease in free energy (downhill), not

spontaneous-increase free energy (uphill)• What is free energy? Energy available to do work. G=H-TS• Maximum amount of free energy that can be harvested

from a reaction is the free energy change of the reaction ( G).

G=H-T S G-energy available to do work (keep cells alive) H-total energy S-energy unavailable to do work

How is G determined for a reaction? FE of products –FE of reactants.

• a. If G is negative (the free energy of the reactants is > fe of products), the reaction is spontaneous (downhill).

• b. If G is positive (the fe of the reactants is < fe of products), the reaction is not spontaneous (uphill).

• c. If G is 0-no free energy difference. The reaction is at equilibrium. No work can be done from that reaction.

Figure 6.5 The relationship of free energy to stability, work capacity, and spontaneous change

LE 8-6a

Reactants

EnergyProducts

Progress of the reaction

Amount ofenergy

released(G < 0)

Fre

e en

erg

y

Exergonic reaction: energy released

LE 8-6b

ReactantsEnergy

Products

Progress of the reaction

Amount ofenergy

required(G > 0)

Fre

e en

erg

y

Endergonic reaction: energy required

Exergonic and Endergonic reactions

• Reactions can also be classified based on free energy changes. Endergonic and exergonic reactions.

Differences in Exergonic and Endergonic Reactions

Metabolic reactions and equilibrium

• What would be the problem for a cell if its metabolic reactions (especially catabolic ones) were allowed to reach equilibrium?

• Cellular metabolism is normally not allowed to reach equilibrium.

• Metabolism generally involves multi-step pathways where the product of one reaction becomes the substrate of the next reaction.

• This strategy only works because cells are open systems

LE 8-7a

G = 0

A closed hydroelectric system

G < 0

LE 8-7b

An open hydroelectric system

G < 0

LE 8-7c

A multistep open hydroelectric system

G < 0G < 0

G < 0

Relationship between catabolic and anabolic reactions

• Coupling endergonic and exergonic reactions

• example.

LE 8-12

Pi

ADP

Energy for cellular work

(endergonic, energy-

consuming processes)

Energy from catabolism

(exergonic, energy-

yielding processes)

ATP

+

LE 8-10

Endergonic 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

+

+ +

LE 8-13

SucroseC12H22O11

GlucoseC6H12O6

FructoseC6H12O6

Enzymes

• Characteristics

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.

LE 8-16

Substrate

Active site

Enzyme Enzyme-substratecomplex

Catalysis

• Properties of a catalyst

• How do enzymes increase the rate of a chemical reaction

• Why don’t enzymes alter the of a reaction?

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

Fre

e en

erg

y

LE 8-15

Course ofreactionwithoutenzyme

EA

without enzyme

G is unaffectedby enzyme

Progress of the reaction

Fre

e en

erg

y

EA withenzymeis lower

Course ofreactionwith enzyme

Reactants

Products

Factors influencing enzyme activity

Factors influencing enzyme activity

• Temperature

• pH

LE 8-18a

Optimal 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 o

f re

acti

on

LE 8-18b

Optimal pH for pepsin(stomach enzyme)

Optimal pHfor trypsin(intestinalenzyme)

pH

Optimal pH for two enzymes

0

Rat

e o

f re

acti

on

1 2 3 4 5 6 7 8 9 10

Factors influencing enzyme activity

Inhibitors:

A. nonreversible

B. Reversible

1. Competitive inhibition

2. Noncompetitive inhibition

LE 8-19a

Substrate

Active site

Enzyme

Normal binding

A substrate canbind normally to the

active site of anenzyme.

LE 8-19b

Competitiveinhibitor

Competitive inhibition

A competitiveinhibitor mimics the

substrate, competingfor the active site.

LE 8-19c

Noncompetitive inhibitor

Noncompetitive inhibition

A noncompetitiveinhibitor binds to the

enzyme away from theactive site, altering the

conformation of theenzyme so that its

active site no longerfunctions.

A practical application of noncompetitive inhibition

• Feedback Inhibition

• Purpose of feedback inhibition

LE 8-UN159

OML

N

S

R

Q

P–

–

–

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)