Introduction to Metabolism

• Metabolism is the sum of an organism’s chemical reactions

• Metabolism is an emergent property of life that arises from interactions between molecules within the cell

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

The product of one reaction is substrate of the next

• Each step is catalyzed by a specific enzyme

BIOCHEMICAL PATHWAYVIDEO

ENZYMES THAT WORK TOGETHER IN A PATHWAY CAN BE

Soluble with free floating intermediates

Covalently bound incomplex

Attached toa membranein sequence

Concentrated in specific

location

CATABOLIC PATHWAY (CATABOLISM)Release of energy by the breakdown of complex molecules to simpler compoundsEX: digestive enzymes break down food

ANABOLIC PATHWAY (ANABOLISM)consumes energy to build complicated molecules from simpler onesEX: linking amino acids to form proteins

Krebs Cycle connects the catabolic and anabolic pathways

Forms of Energy• ENERGY = capacity to cause change

• Energy exists in various forms (some of which can perform work)

• Energy can be converted from one form to another

KINETIC ENERGY – energy associated with motion

–HEAT (thermal energy) is kinetic energy associated with random movement of atoms or molecules

POTENTIAL ENERGY = energy that matter possesses because of its location or structure

–CHEMICAL energy is potential energy available for release in a chemical reaction

On the platform, the diver hasmore potential energy.

Diving convertspotential energy to kinetic energy.

Climbing up converts kinetic energy of muscle movement to potential energy.

In the water, the diver hasless potential energy.

THERMODYNAMICS = the study of energy transformations

• CLOSED system (EX: liquid in a thermos) = isolated from its surroundings

• OPEN system energy + matter can be transferred between the system and its surroundings

• Organisms are open systems

The First Law of Thermodynamics= energy of the universe is constant

–Energy can be transferred and transformed

–Energy cannot be created or destroyed

• The first law is also called the principle of CONSERVATION OF ENERGY

The Second Law of ThermodynamicsDuring every energy transfer or transformation

•entropy (disorder) of the universe INCREASES

•some energy is unusable, often lost as heat

Chemical energy

Heat

CO2

First law of thermodynamics Second law of thermodynamics

H2O

ORGANISMS are energy TRANSFORMERS!

Spontaneous processes occur without energy input; they can happen quickly or slowly

For a process to occur without energy input, it must increase the entropy of the universe

Free-Energy Change (G) can help tell which reactions will happen ∆G = change in free energy ∆H = change in total energy (enthalpy) or change ∆S = entropy T = temperature

∆G = ∆H - T∆S

•Only processes with a negative ∆G are spontaneous

•Spontaneous processes can be harnessed to perform work

Exergonic and Endergonic Reactions in Metabolism• EXERGONIC reactions

(- ∆G)

• Release energy

• are spontaneous

ENDERGONIC reactions (+ ∆G)

• Absorb energy fromtheir surroundings

• are non-spontaneous

Concept 8.3: ATP powers cellular work by coupling exergonic reactions to endergonic reactions• A cell does three main kinds of work:

–Mechanical

–Transport

–Chemical

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

• Overall, the coupled reactions are exergonic

Phosphate groups

Ribose

Adenine

ATP (adenosine triphosphate) is the cell’s renewable and reusable energy shuttle

ATP provides energy for cellular functions

Energy to charge ATP comes from catabolic reactions

Adenosine triphosphate (ATP)

Energy

P P P

PPP i

Adenosine diphosphate (ADP)Inorganic phosphate

H2O

+ +

P

i

ADP

Energy for cellular workprovided by the loss ofphosphate from ATP

Energy from catabolism(used to charge upADP into ATP

ATP

+

Endergonic reaction: DG is positive, reaction is not spontaneous

Exergonic reaction: DG is negative, reaction is spontaneous

G = +3.4 kcal/mol

G = –7.3 kcal/mol

G = –3.9 kcal/mol

NH2

NH3Glu Glu

Glutamicacid

Coupled reactions: Overall DG is negative;Together, reactions are spontaneous

Ammonia Glutamine

ATP H2O ADP P i

+

+ +

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

+ +

+

Every chemical reaction between molecules involves bond breaking and bond forming

ACTIVATION ENERGY = amount of energy required to get chemical reaction started

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

IT’S LIKE PUSHING A SNOWBALL UP A HILL . . . Once you get it up there, it can roll down by itself

Free energy animation

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 e

nerg

y

The Activation Energy Barrier

CATALYST = a chemical agent that speeds up a reaction without being consumed by the reaction

ENZYMES = biological catalystsMost enzymes are PROTEINS Exception = ribozymes (RNA)

Course ofreactionwithoutenzyme

EA

without enzyme

G is unaffectedby enzyme

Progress of the reaction

Fre

e e

nerg

y

EA withenzymeis lower

Course ofreactionwith enzyme

Reactants

Products

ENZYMES work by LOWERING ACTIVATION ENERGY;

ENZYMES LOWER ACTIVATION ENERGY BY:

–Orienting substrates correctly

–Straining substrate bonds

–Providing a favorable microenvironment

Enzymes change ACTIVATION ENERGY

but NOT energy of REACTANTS or PRODUCTS

ENZYMES

• Most are proteins • Lower activation energy• Specific• Shape determines function• Re-usable• Unchanged by reaction

• The REACTANT that an enzyme acts on = SUBSTRATE

• Enzyme + substrate = ENZYME-SUBSTRATE COMPLEX

• Region on the enzyme where the substrate binds = ACTIVE SITE

• Substrate held in active site by WEAK interactions (ie. hydrogen and ionic

bonds)

TWO MODELS PROPOSED• LOCK & KEY

Active site on enzymefits substrate exactly

• INDUCED FITBinding of substrate causes changein active site so it fits substratemore closely

–General environmental factors, such as temperature, pH, salt concentration, etc.

–Chemicals that specifically influence the enzyme

See a movieChoose narrated

Enzyme Activity can be affected by:

TEMPERATURE & ENZYME ACTIVITY

Each enzyme has an optimal temperature at which it can function (Usually near body temp)

Increasing temperature increases the rate of an enzyme-catalyzed reaction up to a point.Above a certain temperature, activity begins to decline because the enzyme begins to denature.

pH and ENZYME ACTIVITYEach enzyme has an optimal pH at which it can

function

COFACTORS = non-protein enzyme helpers

• EX: Zinc, iron, copper

COENZYMES = organic enzyme helpers

• Ex: vitamins

SUBSTRATE CONCENTRATION & ENZYME ACTIVITY

V MAX←

Adding substrate increases activity up to a point

REGULATION OF ENZYME PATHWAYS• GENE REGULATION

cell switches on or off the genes that code for specific enzymes

REGULATION OF ENZYME PATHWAYS• FEEDBACK INHIBITION

end product of a pathway interacts with and “turns off” an enzyme earlier in pathway

• prevents a cell from wasting chemical resources by synthesizing more product than is needed

FEEDBACK INHIBITION

NEGATIVE FEEDBACK–An accumulation of an end product slows the

process that produces that product

B

A

C

D

Enzyme 1

Enzyme 1

Enzyme 2

Enzyme 3

DD D D

D

D

DD

DD

C

B

A Negative feedback

Example: sugar breakdown generates ATP; excess ATP inhibits an enzyme near the beginning of the pathway

POSITIVE FEEDBACK (less common)

–The end product speeds up production

WW

X

Y

Z

ZZ

ZZ

Z

Z Z Z

Z Z Z Z

Z

ZZ Z

ZZ

Y

X

Enzyme 4

Enzyme 5

Enzyme 6

Enzyme 4

Enzyme 5

Enzyme 6

Positivefeedback

EXAMPLE: Chemicals released by platelets that accumulate at injury site, attract MORE platelets to the site.

REGULATION OF ENZYME ACTIVITY• ALLOSTERIC REGULATION

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

• Allosteric regulation can inhibit or stimulate an enzyme’s activity

Allosteric enzyme inhibition

SOME ALLOSTERIC ENZYMES HAVE MULTIPLE SUBUNITS

• Each enzyme has active and inactive forms

• The binding of an ACTIVATOR stabilizes the active form

• The binding of an INHIBITOR stabilizes the inactive form

Substrate

Binding of one substrate molecule to active site of one subunit locks allsubunits in active conformation.

COOPERATIVITY another type of allosteric activation

Stabilized active formInactive form

COOPERATIVITY = form of allosteric regulation that can amplify enzyme activity

Binding of one substrate to active site of one subunit locks all subunits in active conformation

COMPETITIVE inhibitor REVERSIBLE; Mimics substrate and competes with substrate for active site on enzyme

ENZYMEANIMATION

Enzyme Inhibitors

Enzyme InhibitorsNONCOMPETITIVE inhibitors bind to another part

of an enzyme, causing the enzyme to change shape and making the active site less effective

ENZYMEANIMATION