An IntroductionAn Introductionto Metabolismto Metabolism

Metabolism = Catabolism + Anabolism

Catabolic reactions are energy yielding

•They are involved in the breakdown of more-complex molecules into simpler ones

Anabolic reactions are energy requiring

•They are involved in the building up of simpler molecules into more-complex ones

Introduction to Metabolism

“Energy can be transferred or

transformed but neither created nor destroyed.”

“Every energy transfer or transformation increases the

disorder (entropy) of the universe.”

Note especially the waste heat

First and Second Laws of ThermodynamicsFirst and Second Laws of Thermodynamics

Organisms take in energy & transduce it to new forms (1st law)

As energy transducers, organisms are less than 100% efficient (2nd law)

Organisms employ this energy to:• Grow• Protect Themselves• Repair Themselves• Compete with other Organisms• Make new Organisms (I.e., babies) In the process, organisms generate waste

chemicals & heat Organisms create local regions of order at

the expense of the total energy found in the Universe!!! We are Energy Parasites!

Energy in the Biosphere

Kinetic and Potential Energy

First Law of Thermodynamics:

•Energy can be neither created nor destroyed

•Therefore, energy “generated” in any system is energy that has been transformed from one state to another (e.g., chemically stored energy transformed to heat)

Second Law of Thermodynamics:

•Efficiencies of energy transformation never equal 100%

•Therefore, all processes lose energy, typically as heat, and are not reversible unless the system is open & the lost energy is resupplied from the environment

•Conversion to heat is the ultimate fate of chemical energy

DownhillIncrease stability

Greater entropy

G < 0

What is the name of this molecule?

Free Energy and SpontaneityFree Energy and Spontaneity

Potential energy

Work

Spontaneous

Equilibrium

Forward reaction

EquilibriumEquilibrium

Potential energy

Work

Spontaneous“Food”

Forward reaction

Waste heat

Note that “Spontaneity” is not a measure of speed of a

process, only its direction

Movement towards Equilibrium in Movement towards Equilibrium in StepsSteps

Energy released

“Food”

Movement toward equilibrium

Exergonic ReactionsExergonic Reactions

Energy required

“Work”

Endergonic reactionsEndergonic reactions

Exergonic Reaction (Spontaneous)Exergonic Reaction (Spontaneous)• Decrease in Gibbs free energy (-G)• Increase in stability• Spontaneous (gives off net energy upon going forward)• Downhill (toward center of gravity well, e.g., of Earth)• Movement towards equilibrium• Coupled to ATP production (ADP phosphorylation)• Catabolism

Endergonic Reaction (Non-Spontaneous)• Increase in Gibbs free energy (+G)• Decrease in stability• Not Spontaneous (requires net input of energy to go forward)• Uphill (away from center of gravity well, e.g., of Earth)• Movement away from equilibrium• Coupled to ATP utilization (ATP dephosphorylation)• Anabolism

Cou

plin

g R

eact

ions

Cou

plin

g R

eact

ions

Exergonic reactions can supply energy for endergonic

reactions

Ene

rgy

Cou

plin

g in

Met

abol

ism

Ene

rgy

Cou

plin

g in

Met

abol

ism

Catabolic reaction

Anabolic reaction

Catabolic reactions provide the energy that drives anabolic reactions forward

Adenosine Triphosphate (ATP)Adenosine Triphosphate (ATP)

Energy Coupling via ATPEnergy Coupling via ATP

Hydrolysis of Hydrolysis of ATPATP

Cou

pled

Rea

ctio

nsC

oupl

ed R

eact

ions

Var

ious

Pi T

rans

fers

Var

ious

Pi T

rans

fers

Summary of Metabolic Summary of Metabolic CouplingCoupling

Endergonic reaction

Exergonic reaction

Exergonic reaction

Endergonic reaction

Exergonic processes drive Endergonic processes

Anabolic process

Catabolic process

Chemically stored energy

Enzyme Catalyzed Enzyme Catalyzed ReactionReaction

Question: Is this reaction

endergonic or is it exergonic?

Enzyme

Act

ivat

ion

Ene

rgy

(EA

ctiv

atio

n E

nerg

y (E

AA)) Anything that

doesn’t require an input of

energy to get started has

already happened!

Low

- (i.

e., b

ody-

) T

emp.

Sta

bilit

yLo

w-

(i.e.

, bod

y-)

Tem

p. S

tabi

lity

Why don't energy-rich molecules, e.g., glucose, spontaneously degrade into CO2 and Water?

• To be unstable, something must have the potential to change into something else, typically something that possesses less free energy

• To be unstable, releasing something’s ability to change into something else must also be relatively easy (i.e., little input energy)

• Therefore, stability = already low free energy

• Alternatively, stability = high activation energy

Things, therefore, can be high in free energy but still quite stable, e.g., glucose

CatalysisCatalysis

Lowering of activation

energy

CatalysisCatalysis

At a given temperature,

catalyzed reactions can run faster

because less energy is required to achieve

the transition state

This is instead of adding heat; heat is an inefficient means

of speeding up reactions since it

simply is a means of increasing the

random jostlings of molecules

Enz

yme-

med

iate

d C

atal

ysis

Enz

yme-

med

iate

d C

atal

ysis

= Subtle application of energy

Mec

hani

sms

of

Mec

hani

sms

of

Cat

alys

isC

atal

ysis

Active sites can hold two or more substrates in proper orientations so that new bonds between substrates can form

Active sites can stress the substrate into the transition state

Active sites can maintain conducive physical environments (e.g., pH)

Active sites can participate directly in the reaction (e.g., forming transient covalent bonds with substrates)

Active sites can carry out a sequence of manipulations in a defined temporal order (e.g., step A step B step C)

Catalysis as Viewed in 3DCatalysis as Viewed in 3D

Active site is site of

catalysis

The rest of an enzyme is involved in

supporting active site, controlling reaction rates,

attaching to other things, etc.

Indu

ced

Fit

(Act

ive

Indu

ced

Fit

(Act

ive

Site

)S

ite)

Induced fit not only allows the enzyme to bind the substrate(s), but also provides a subtle application of energy (e.g., “bending” chemical bonds) that causes the substrate(s) to destabilize into the transition state

Enz

yme

Sat

urat

ion

Enz

yme

Sat

urat

ion Substr

ateProduct

Enzyme Activity at Saturation is a Function of Enzyme Turnover Rate

Enz

yme

Sat

urat

ion

Enz

yme

Sat

urat

ion

Turnover rate

Non-Specific Inhibition of Enzyme Non-Specific Inhibition of Enzyme ActivityActivity

Instability & shape change

(too fluid)

Reduced rate of chemical

reaction

Reduced enzyme fluidity

Change in R group

ionization

Change in R group

ionization

Denatured?

Turnover rate

Even at saturation, rates of enzymatic reactions

can be modified

Activators of CatalysisActivators of CatalysisMetal Ion or =Organic Molecule

= OrganicCofactor

Spe

cific

S

peci

fic

Inhi

bitio

nIn

hibi

tion

Competitive inhibitors can be competed

off by supplying sufficient substrate densities

Non-competitive inhibitors cannot be competed off

by substrate

Allo

ster

ic

Allo

ster

ic

Inte

ract

ions

Inte

ract

ions

Reversible interactions,

sometimes on, sometimes off, dependent on

binding constant and

density of effector

CooperativityCooperativityCooperativity is when the activity of

other subunits are increased by

substrate binding to

one subunit’s active site

Fee

dbac

k In

hibi

tion

Fee

dbac

k In

hibi

tion

Energy-Metabolism Energy-Metabolism RegulationRegulation

Enz

yme

Loca

lizat

ion

Enz

yme

Loca

lizat

ion

Organization of Electron

Transport Chain of Cellular

Respiration

Enzymes in single pathway may be co-localized so that the product of one enzyme

increases the local concentration of the substrate for another

The EndThe End