Ch.8An

Introduction to Metabolism

Flow of energy through lifeFlow of energy through life

• Life is built on chemical reactions– transforming energy from one form to another

organic molecules ATP & organic molecules

organic molecules ATP & organic molecules

sun

solar energy ATP & organic molecules

Metabolism

– Is the totality of an organism’s chemical reactions

Organization of the Chemistry of Life into Organization of the Chemistry of Life into Metabolic PathwaysMetabolic Pathways

A metabolic pathway begins with a specific molecule and ends with a product

Each step is catalyzed by a specific enzyme

Startingmolecule

Product

Enzyme 1 Enzyme 2 Enzyme 3

B CA D

MetabolismMetabolism• Chemical reactions of life

– forming bonds between molecules• dehydration synthesis

• synthesis

• anabolic reactions

– breaking bonds between molecules• hydrolysis

• digestion

• catabolic reactions

That’s why they’re calledanabolic steroids!

ThermodynamicsThermodynamics• Energy (E)~ capacity to do work; Kinetic energy~ energy of motion;

Potential energy~ stored energy

• Thermodynamics~ study of E transformations

• 1st Law: conservation of energy; E transferred/transformed, not created/destroyed

• 2nd Law: transformations increase entropy (disorder, randomness)

Free energyFree energy

• Free energy: portion of system’s E that can perform work (at a constant T)

• Exergonic reaction: net release of free E to surroundings

• Endergonic reaction: absorbs free E from surroundings

Change in free energy, ∆G

• The change in free energy, ∆G during a biological process– Is related directly to the enthalpy

change (∆H) and the change in entropy (∆S)

∆G = ∆H – T∆S

T = temp in Kelvin (K)

Chemical reactions & energyChemical reactions & energy• Some chemical reactions release energy

– exergonic– ∆G < 0– spontaneous– digesting polymers– hydrolysis = catabolism

digesting molecules= LESS organization=lower energy state

Figure 8.6

Reactants

ProductsEnergy

Progress of the reaction

Amount ofenergyreleased (∆G <0)

Fre

e e

ne

rgy

(a) Exergonic reaction: energy released

Chemical reactions & energyChemical reactions & energy• Some chemical reactions require input of energy

– endergonic– ∆G > 0– non-spontaneous– building polymers – dehydration synthesis = anabolism

building molecules= MORE organization=higher energy state

Figure 8.6

Energy

Products

Amount ofenergyreleased (∆G>0)

Reactants

Progress of the reaction

Fre

e e

ne

rgy

(b) Endergonic reaction: energy required

The energy needs of lifeThe energy needs of life• Organisms are endergonic systems

– What do we need energy for?• synthesis

– building biomolecules

• reproduction• movement• active transport• temperature regulation

Where do we get the energy from?Where do we get the energy from?• Work of life is done by energy coupling

– use exergonic (catabolic) reactions to fuel endergonic (anabolic) reactions

+ + energy

+ energy+

digestion

synthesis

ATP

Living economyLiving economy• Fueling the body’s economy

– eat high energy organic molecules • food = carbohydrates, lipids, proteins, nucleic acids

– break them down• digest = catabolism

– capture released energy in a form the cell can use

• Need an energy currency– a way to pass energy around

– need a short term energy storage molecule

Whoa! Hot stuff!

ATPATP

high energy bondsHow efficient!Build once,use many ways

• Adenosine TriPhosphate– modified nucleotide

• nucleotide = adenine + ribose + Pi AMP

• AMP + Pi ADP• ADP + Pi ATP

– adding phosphates is endergonic

How does ATP store energy?How does ATP store energy?

PO–

O–

O

–O PO–

O–

O

–O PO–

O–

O

–OPO–

O–

O

–O PO–

O–

O

–OPO–

O–

O

–O PO–

O–

O

–O PO–

O–

O

–O

• Each negative PO4 more difficult to add– a lot of stored energy in each bond

• most energy stored in 3rd Pi

• 3rd Pi is hardest group to keep bonded to molecule

• Bonding of negative Pi groups is unstable– spring-loaded– Pi groups “pop” off easily & release energy

Instability of its P bonds makes ATP an excellent energy donor

I thinkhe’s a bitunstable…don’t you?

AMPAMPADPATP

How does ATP transfer energy? How does ATP transfer energy?

PO–

O–

O

–O PO–

O–

O

–O PO–

O–

O

–O7.3energy+P

O–

O–

O

–O

• ATP ADP– releases energy

• ∆G = -7.3 kcal/mole

• Fuel other reactions• Phosphorylation

– released Pi can transfer to other molecules• destabilizing the other molecules

– enzyme that phosphorylates = “kinase”

ADPATP

It’snever thatsimple!

An example of Phosphorylation…An example of Phosphorylation…

• Building polymers from monomers– need to destabilize the monomers

– phosphorylate!

C

H

OH

H

HOC C

H

O

H

C+ H2O++4.2 kcal/mol

C

H

OHC

H

P+ ATP + ADP

H

HOC+ C

H

O

H

CC

H

P+ Pi

“kinase” enzyme

-7.3 kcal/mol

-3.1 kcal/mol

enzyme

H

OHC

H

HOC

synthesis

Can’t store ATP good energy donor,

not good energy storagetoo reactivetransfers Pi too easilyonly short term energy storage

carbohydrates & fats are long term energy storage

ATP / ADP cycleATP / ADP cycle

A working muscle recycles over 10 million ATPs per second

Whoa!Pass methe glucose(and O2)!

ATP

ADP Pi+

7.3 kcal/mole

cellularrespiration

Another example of Phosphorylation…Another example of Phosphorylation…

• The first steps of cellular respiration– beginning the breakdown of glucose to make ATP

glucoseC-C-C-C-C-C

fructose-1,6bPP-C-C-C-C-C-C-P

DHAPP-C-C-C

G3PC-C-C-P

hexokinase

phosphofructokinase

Thosephosphatessure make ituncomfortablearound here!

C

H

P

C

P

CATP2

ADP2

activationenergy

Too much activation energy for lifeToo much activation energy for life

• Activation energy– amount of energy needed to destabilize the

bonds of a molecule– moves the reaction over an “energy hill”

glucose

Reducing Activation energyReducing Activation energy• Catalysts

– reducing the amount of energy to start a reaction

Pheeew…that takes a lotless energy!

reactant

product

uncatalyzed reaction

catalyzed reaction

NEW activation energy

CatalystsCatalysts• So what’s a cell got to do to reduce

activation energy?– get help! … chemical help… ENZYMES

G

Call in the ENZYMES!

Substrate Specificity of Enzymes

• The substrate– Is the reactant an enzyme acts on

• The enzyme– Binds to its substrate, forming an

enzyme-substrate complex

• The active site– Is the region on the enzyme

where the substrate binds

Figure 8.16

Substrate

Active site

Enzyme

(a)

Naming conventionsNaming conventions• Enzymes named for reaction they catalyze

– sucrase breaks down sucrose

– proteases break down proteins

– lipases break down lipids

– DNA polymerase builds DNA• adds nucleotides

to DNA strand

– pepsin breaks down proteins (polypeptides)

Factors Affecting Enzyme FunctionFactors Affecting Enzyme Function• Enzyme concentration

• Substrate concentration

• Temperature

• pH

• Salinity

• Activators

• Inhibitors

catalase

Factors affecting enzyme function Factors affecting enzyme function • Enzyme concentration

– as enzyme = reaction rate• more enzymes = more frequently collide with substrate

– reaction rate levels off• substrate becomes limiting factor• not all enzyme molecules can find substrate

enzyme concentration

reac

tion

rat

e

Factors affecting enzyme function Factors affecting enzyme function

substrate concentration

reac

tion

rat

e

• Substrate concentration – as substrate = reaction rate

• more substrate = more frequently collide with enzyme

– reaction rate levels off• all enzymes have active site engaged• enzyme is saturated• maximum rate of reaction

Factors affecting enzyme functionFactors affecting enzyme function• Temperature

– Optimum T° • greatest number of molecular collisions• human enzymes = 35°- 40°C

– body temp = 37°C

– Heat: increase beyond optimum T°• increased energy level of molecules disrupts bonds in

enzyme & between enzyme & substrate– H, ionic = weak bonds

• denaturation = lose 3D shape (3° structure)– Cold: decrease T°

• molecules move slower • decrease collisions between enzyme & substrate

Enzymes and temperatureEnzymes and temperature• Different enzymes function in different

organisms in different environments

37°Ctemperature

reac

tion

rat

e

70°C

human enzymehot springbacteria enzyme

(158°F)

Factors affecting enzyme functionFactors affecting enzyme function• pH

– changes in pH• adds or remove H+

• disrupts bonds, disrupts 3D shape – disrupts attractions between charged amino acids – affect 2° & 3° structure– denatures protein

– optimal pH?• most human enzymes = pH 6-8

– depends on localized conditions– pepsin (stomach) = pH 2-3– trypsin (small intestines) = pH 8

720 1 3 4 5 6 8 9 10 11

Factors affecting enzyme functionFactors affecting enzyme function• Salt concentration

– changes in salinity• adds or removes cations (+) & anions (–)

• disrupts bonds, disrupts 3D shape – disrupts attractions between charged amino acids

– affect 2° & 3° structure

– denatures protein

– enzymes intolerant of extreme salinity• Dead Sea is called dead for a reason!

Enzyme cofactors

• Cofactors– Are non-protein enzyme helpers e.g.

zinc, iron, copper atoms

• Coenzymes– Are organic cofactors e.g. vitamins

 coenzymes in group transfer

reactions

 coenzyme  abbreviation  entity transfered

 nicotine adenine

dinucelotide

 NAD - partly composed of

niacin

 electron (hydrogen atom)

 nicotine adenine

dinucelotide phosphate

 NADP -Partly composed of

niacin

 electron (hydrogen atom)

 flavine adenine

dinucelotide

 FAD - Partly composed of

riboflavin (vit. B2)

 electron (hydrogen atom)

 coenzyme A  CoA  Acyl groups        

 coenzymeQ  CoQ electrons

(hydrogen atom)

Enzyme Regulation

• Regulation of enzyme activity helps control metabolism

• A cell’s metabolic pathways– Must be tightly regulated

Enzyme Inhibitors• Competitive

inhibitors– Bind to the active

site of an enzyme, competing with the substrate

Figure 8.19 (b) Competitive inhibition

A competitiveinhibitor mimics the

substrate, competingfor the active site.

Competitiveinhibitor

A substrate canbind normally to the

active site of anenzyme.

Substrate

Active site

Enzyme

(a) Normal binding

Enzyme Inhibitors

• Noncompetitive inhibitors– Bind to another part of an enzyme,

changing the 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

Allosteric regulationAllosteric regulation• Conformational changes by regulatory

molecules – inhibitors

• keeps enzyme in inactive form

– activators • keeps enzyme in active form

Conformational changes Allosteric regulation

Feedback inhibition

– The end product of a metabolic pathway shuts down the pathway

Active siteavailable

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

Cooperativity Cooperativity • Substrate acts as an activator

– substrate causes conformational change in enzyme

• induced fit

– favors binding of substrate at 2nd site

– makes enzyme more active & effective

• hemoglobin

Hemoglobin 4 polypeptide chains can bind 4 O2; 1st O2 binds now easier for other 3

O2 to bind