essential knowledge 2a.1b. living systems do not violate the second law of thermodynamics, which...

Essential Knowledge 2A.1b. Living systems do not violate the second law of thermodynamics, which states that entropy increases over time.

• Evidence of student learning is a demonstrated understanding of each of the following:

1. Order is maintained by coupling cellular processes that increase entropy (and so have negative changes in free energy) with those that decrease entropy (and so have positive changes in free energy).

2. Energy input must exceed free energy lost to entropy to maintain order and power cellular processes.

3. Energetically favorable exergonic reactions, such as ATP→ADP, that have a negative change in free energy can be used to maintain or increase order in a system by being coupled with reactions that have a positive free energy change.

Energy and Matter converted from concentrated to less concentrated forms…

Simple Molecule

Concentrated Energy

More ordered molecule

Heat

Entropy of universe increased

Previous slide Picture can be summarized by the following:

• Cells create ordered structures from less ordered materials using energy

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

• Energy flows into an ecosystem in the form of light and exits in the form of heat

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

∆G = ∆H – T∆S

∆G: The change in free energy during a process

∆H: change in total energy, or enthalpy

∆S: change in entropy (disorder)

T: temperature in Kelvin.

• Spontaneous processes have a negative ∆G (-∆G )

• To be spontaneous reactions must give up ENERGY (-∆H), ORDER (T∆S) or BOTH!


Free energy: how much energy is available to do work from a given reaction.

• Free energy is a measure of a system’s instability, its tendency to change to a more stable state (equilibrium)

• A process is spontaneous and can perform work only when it is moving toward equilibrium

• During a spontaneous change, free energy decreases and the stability of a system increases


Free Energy, Stability, and 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• -∆G • 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

Free Energy and Metabolism

• The concept of free energy can be applied to the chemistry of life’s processes


• Exergonic reaction: release free energy, (-∆G ) and is spontaneous

• Catabolic pathways

• Endergonic reaction: absorbs free energy, (+∆G )

and is nonspontaneous

• Anabolic pathways

Spontaneous in the direction

shown

Fig. 8-6

Reactants

Energy

Fre

e e

ne

rgy

Products

Amount ofenergy

released(∆G < 0)

Progress of the reaction

(a) Exergonic reaction: energy released

Products

ReactantsEnergy

Fre

e e

ne

rgy

Amount ofenergy

required(∆G > 0)

(b) Endergonic reaction: energy required


Exergonic and Endergonic Reactions

Example Glucose 686 kcal/ mol

Equilibrium and Metabolism

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

• Cells are open systems and never reach equilibrium

• Example: The catabolic pathway of breaking down glucose into CO2 and H2O


∆G < 0 ∆G = 0

∆G < 0

∆G < 0

∆G < 0

∆G < 0

Fig. 8-7

(a)An isolated hydroelectric system

(b) An open hydroelectric system

(c) A multistep open hydroelectric system

Analogy for catabolic pathways

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

• A cell does three main kinds of work:

– Chemical

– Transport

– Mechanical

• Energy coupling: the use of an exergonic process to drive an endergonic one

• ATP is used for most coupling in cells.


The Structure and Hydrolysis of ATP

• ATP (adenosine triphosphate) is the cell’s energy shuttle

• ribose (a sugar), adenine (a nitrogenous base), and three phosphate groups


Phosphate groupsRibose

Adenine

Fig. 8-9

Inorganic phosphate

Energy

Adenosine triphosphate (ATP)

Adenosine diphosphate (ADP)

P P

P P P

P ++

H2O

i

Hydrolysis of ATP releases energy

How ATP Performs Work

• Cellular work is powered by hydrolysis of ATP

• The energy from the exergonic reaction of ATP hydrolysis can be used to drive an endergonic reaction

• Overall, the coupled reactions are exergonic


Fig. 8-10

(b) Coupled with ATP hydrolysis, an exergonic reaction

Ammonia displacesthe phosphate group,forming glutamine.

(a) Endergonic reaction

(c) Overall free-energy change

PP

GluNH3

NH2

Glu i

GluADP+

PATP+

+

Glu

ATP phosphorylatesglutamic acid,making the aminoacid less stable.

GluNH3

NH2

Glu+

Glutamicacid

GlutamineAmmonia

∆G = +3.4 kcal/mol

+2

1

Fig. 8-11

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

Membrane protein

P i

ADP+

P

Solute Solute transported

Pi

Vesicle Cytoskeletal track

Motor protein Protein moved

(a) Transport work: ATP phosphorylates transport proteins

ATP

ATP

Fig. 8-12

P iADP +

Energy fromcatabolism (exergonic,energy-releasingprocesses)

Energy for cellularwork (endergonic,energy-consumingprocesses)

ATP + H2O

The Regeneration of ATP

Essential knowledge 4.B.1: Interactions between molecules affect their structure and function.

• a. Change in the structure of a molecular system may result in a change of the function of the system.

• b. The shape of enzymes, active sites and interaction with specific molecules are essential for basic functioning of the enzyme.

• Evidence of student learning is a demonstrated understanding of each of the following:

– 1. For an enzyme-mediated chemical reaction to occur, the substrate must be complementary to the surface properties (shape and charge) of the active site. In other words, the substrate must fit into the enzyme’s active site.

– 2. Cofactors and coenzymes affect enzyme function; this interaction relates to a structural change that alters the activity rate of the enzyme. The enzyme may only become active when all the appropriate cofactors or coenzymes are present and bind to the appropriate sites on the enzyme.

• c. Other molecules and the environment in which the enzyme acts can enhance or inhibit enzyme activity. Molecules can bind reversibly or irreversibly to the active or allosteric sites, changing the activity of the enzyme.

• d. The change in function of an enzyme can be interpreted from data regarding the concentrations of product or substrate as a function of time. These representations demonstrate the relationship between an enzyme’s activity, the disappearance of substrate, and/ or presence of a competitive inhibitor.

Concept 8.4: Enzymes speed up metabolic reactions by lowering energy barriers

• A catalyst is a chemical that speeds up a reaction without being consumed by the reaction

• An enzyme is a catalytic protein


Sucrose (C12H22O11)

Glucose (C6H12O6) Fructose (C6H12O6)

Sucrase

The Activation Energy Barrier

• Chemical reactions rearrange bonds

• The energy needed to start a chemical reaction is called the activation energy (EA)

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



Products

Reactants

∆G < O

Transition state

Fre

e e

ner

gy

EA

DC

BA

D

D

C

C

B

B

A

A

How Enzymes Lower the EA Barrier

• Enzymes catalyze reactions by lowering the EA barrier

• Enzymes do not affect the change in free energy (∆G) or the point of equilibrium, instead, they hasten reactions that would occur eventually

Animation: How Enzymes WorkAnimation: How Enzymes Work


Fig. 8-15


Products

Reactants

∆G is unaffectedby enzyme

Course ofreactionwithoutenzyme

Fre

e en

erg

y

EA

withoutenzyme EA with

enzymeis lower

Course ofreactionwith enzyme

Substrate Specificity of Enzymes


Substrate

Enzyme-Substrate Complex

Induced fit, enzyme

shape changes to fit the substrate better

Product (s)

Enzyme

Fig. 8-16

Substrate

Active site

Enzyme Enzyme-substratecomplex

(b)(a)This shows the induced fit of

the enzyme- substrate complex.

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


Fig. 8-17

Substrates

Enzyme

Products arereleased.

Products

Substrates areconverted toproducts.

Active site can lower EA

and speed up a reaction.

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

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

Activesite is

availablefor two new

substratemolecules.

Enzyme-substratecomplex

5

3

21

6

4

Conditions that effect enzyme activity

• An enzyme’s activity can be affected by anything that alters the 3D structure of the protein.

– Temperature

– pH

• Many enzymes will not work without Cofactors or Coenzymes

– Cofactors are nonprotein enzyme helpers

– Cofactors may be inorganic (such as a metal in ionic form)

– Coenzyme is an organic cofactorCopyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig. 8-18

Ra

te o

f re

ac

tio

n

Optimal temperature forenzyme of thermophilic

(heat-tolerant) bacteria

Optimal temperature fortypical human enzyme

(a) Optimal temperature for two enzymes

(b) Optimal pH for two enzymes

Ra

te o

f re

ac

tio

n

Optimal pH for pepsin(stomach enzyme)

Optimal pHfor trypsin(intestinalenzyme)

Temperature (ºC)

pH543210 6 7 8 9 10

0 20 40 80 60 100

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

• Examples of inhibitors include toxins, poisons, pesticides, and antibiotics


Fig. 8-19

(a) Normal binding (c) Noncompetitive inhibition(b) Competitive inhibition

Noncompetitive inhibitor

Active siteCompetitive inhibitor

Substrate

Enzyme

Concept 8.5: Regulation of enzyme activity helps control metabolism

• Cells regulate enzyme function by

– Switching on or off the genes that encode specific enzymes

– Regulating the activity of enzymes

• Allosteric Regulation of Enzymes:

– May inhibit or activte an enzyme’s activity

– What happens: Regulatory molecule binds to a protein at one site and affects the protein’s function at another site


Fig. 8-20a

(a) Allosteric activators and inhibitors

InhibitorNon-functionalactivesite

Stabilized inactiveform

Inactive form

Oscillation

Activator

Active form Stabilized active form

Regulatorysite (oneof four)

Allosteric enzymewith four subunits

Active site(one of four)

1. Each enzyme has active and inactive forms

2. The binding of an activator stabilizes the active form of

the enzyme

3. The binding of an inhibitor stabilizes the inactive form of

the enzyme

• 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


(b) Cooperativity: another type of allosteric activation

Stabilized activeform

Substrate

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 needed


Fig. 8-22

Intermediate C

Feedbackinhibition

Isoleucineused up bycell

Enzyme 1(threoninedeaminase)

End product(isoleucine)

Enzyme 5

Intermediate D

Intermediate B

Intermediate A

Enzyme 4

Enzyme 2

Enzyme 3

Initial substrate(threonine)

Threoninein active site

Active siteavailable

Active site ofenzyme 1 nolonger bindsthreonine;pathway isswitched off.

Isoleucinebinds toallostericsite

Interpreting Enzyme Activity Graphs

• Enzyme activity is measured by concentration of substrate and/ or product.

Michaelis Menten Plot

A graph of enzyme kinetics Vmax represents the maximum velocity of the enzyme when all available active sites are bound with substrateKm of the Michaelis constant, the point at which ½ of the active sites are bound with the substrateA LOW km indicates that relatively low amounts of substrate are needed to bind ½ the active site and thus a HIGH affinity for the substrateA HIGH km indicates that a high amounts of substrate are needed and a LOW affinity for the substrate

How would a competitive inhibitor change the MM plot?

Competitive inhibitors change the km of the enzyme

Explanation: The competitive inhibitor competes with the substrate for binding to the active site. As the amount of substrate increases there is more substrate proportionally than inhibitor to bind with the active site. Eventually the amount of substrate overwhelms the competitive inhibitor and the same Vmax is reached as was observed without the inhibitor present. Thus Vmax is not shifted, but the graph is shifted to the right because more substrate is necessary to reach Vmax.

Allosteric affects on enzyme kinetics:

• Allosteric regulation affects the shape of the active site and will change the km, but not Vmax

Answer C

Answer A

Answer D

Review Questions

1. Distinguish between the following pairs of terms:

A. catabolic and anabolic pathways;

B. kinetic and potential energy;

C. open and closed systems;

D. 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. Give three examples of how ATP performs cellular work and explain.

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. Explain the parts of a M-M plat including substrate concentration, Vmax, ½ Vmax and km.

8. Why does the M-M graph level off when substrate concentration is high?

9. Describe how competitive inhibitors affect enzyme function (Draw a picture) and the km of a M-M plot (Draw a picture).

10. Describe how allosteric regulators may inhibit or stimulate the activity of an enzyme (Draw a picture)


Fig. 8-UN5

11. What is the process shown in the diagram below? Why do cells use this type of regulation?

12. What would happen to the production of substance R and S if there was an abundance of substance Q?

13. Which reaction would prevail if both Q and S were present in the cell in high concentrations?

essential knowledge 2a.1b. living systems do not violate the second law of thermodynamics, which...

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