An Introduction to Metabolism

Ch. 8

AP Biology

Ms. Haut

Metabolic Pathways Catabolic Pathways

Release energy by breaking down complex molecules into simpler ones

Cellular respiration provides energy for cellular work

C6H12O6 + 6O2 6CO2 + 6H2O + energy Energy released drives anabolic reactions

Metabolic Pathways Anabolic Pathways

Consume energy by building molecules Photosynthesis uses energy 6CO2 + 6H2O energy C6H12O6 + 6O2

Organisms Transform Energy

Solar Energy

(EK)

Plants (glucose)Stored in

chemical bonds(EP)

AnimalsBreak down

Sugars;Some used (EK), some stored in chemical bonds

(EP)

Energy

Kinetic energy is energy associated with motion Heat (thermal energy) is

kinetic energy associated with random movement of atoms or molecules

Potential energy is energy that matter possesses because of its location or structure Chemical energy is potential

energy available for release in a chemical reaction

Energy can be converted from one form to another

On 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.

Laws of Thermodynamics First Law—Energy can be transferred, but never

created or destroyed Second Law—Every energy transfer results in

increased entropy (randomness in the universe) Some of the energy is converted to heat Reactions occur spontaneously

Chemical energy

Heat CO2

First law of thermodynamics Second law of thermodynamics

H2O

Free Energy

Organisms live at the expense of free energy (portion of a system’s energy available for work) acquired from the surroundings

Free energy is needed for spontaneous changes to occur

Gibbs-Helmholtz Equation

Can be used to determine if a reaction is spontaneous

Spontaneous reactions occur in systems moving from instability to stability

G = H - TSFree

energyTotal

energy

enthalpy

Temp(K)

entropy

Highenergy

Low energy

Gibbs-Helmholtz Equation

In chemical reactions, reactions absorb energy to break bonds

Energy is then released when bonds form between rearranged atoms of the product

G = H - T SMeasure of heatin the

reaction

Key Importance of G Indicates amount of energy available for work Indicates whether a reaction will occur

spontaneously (low G) G decreases as reaction approaches equilibrium G increases as reaction moves away equilibrium G = 0 when a reaction is in equilibrium

Chemical ReactionsExergonic Endergonic

Chemical products have lower G than reactants

Products store more G than reactants

Reaction releases energy Reaction requires energy input (absorbs)

G = negative value G = positive value

Spontaneous Non spontaneous

In cellular metabolism, exergonic reactions drive In cellular metabolism, exergonic reactions drive endergonic reactionsendergonic reactions

Rate of Reactions G indicates spontaneity not speed of reaction Spontaneous reactions will occur if it releases free

energy (- G ), but may occur too slowly to be effective in living cells Can leave sucrose in sterile water for yrs. with hydrolysis

occuring; add sucrase and reaction will hydrolyze in seconds

Biochemical reactions require enzymes to speed up and control reaction rates

ATP couples exergonic reactions to endergonic reactions

A cell does three main kinds of work: Mechanical Transport Chemical

To do work, cells manage energy resources by energy coupling, the use of an exergonic process to drive an endergonic one

ATP Powers Cellular WorkUnstable Bonds—can release energy when broken

Energy transferred toanother molecule (phos-phorylated intermediate) with the phosphate

Less stable More stable

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

+ +

+

The Regeneration of ATP ATP is a renewable resource that is regenerated by

addition of a phosphate group to ADP• The energy to phosphorylate ADP comes from catabolic

reactions in the cell• The chemical potential energy temporarily stored in ATP

drives most cellular work

Pi

ADP

Energy for cellular work

(endergonic, energy-

consuming processes)

Energy from catabolism

(energonic, energy-

yielding processes)

ATP

+ Pi

ADP

Energy for cellular work

(endergonic, energy-

consuming processes)

Energy from catabolism

(energonic, energy-

yielding processes)

ATP

+

Enzymes

Catalyst—chemical agent that speeds up a chemical reaction without being consumed by the reaction

Hydrolysis of sucrose by the enzyme sucrase is an example of an enzyme-catalyzed reaction

SucroseC12H22O11

GlucoseC6H12O6

FructoseC6H12O6

The Activation Energy Barrier Every chemical reaction

between molecules involves bond breaking and bond forming

The initial energy needed to start a chemical reaction is called the free energy of activation, or activation energy (EA)

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

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

Enzymes Catalytic proteins that speed up metabolic

reactions by lowering energy barriers

1. Reactants must absorb energy to reach transition state (unstable)

2. Rxn occurs and energy is released as new bonds form to make products

3. G for overall rxn is difference b/w G of products and G of reactants

Substrate Specificity of Enzymes Substrate—reactant that an enzyme acts Substrate binds to the active site on the enzyme Induced fit of a substrate brings chemical groups of

the active site into positions that enhance their ability to catalyze the reaction

Induced Fit Model of Enzymatic Reactions

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 thetransition state,

• providing a favorablemicroenvironment,

• participating directly in thecatalytic reaction.

Substrates areconverted intoproducts.

Products arereleased.

Activesite is

availablefor two new

substratemolecules.

How do Enzymes Work? Active site holds 2 or more reactants in the

proper position to react Induced fit may distort chemical bonds so

less thermal energy is needed to break them

Active site may provide micro-environment that aids a reaction (localized pH)

Side chains of amino acids in active site may participate in reaction

Enzyme Activity

A cell’s physical and chemical environment affects enzyme activity

Each enzyme has optimal environmental conditions that favor the most active enzyme conformation

Effects of Temperature

Optimal temp. allows greatest number of molecular collisions without denaturing the enzyme

Reaction rate when temperature Kinetic energy increases and collisions increases Beyond optimal temperature, reaction rate slows

Too low, collisions b/w substrate and active site don’t occur fast enough

Too high, agitation disrupts weak bonds of the tertiary structure of enzyme (enzyme unfolds)

Effects of pH

Optimal pH range for most enzymes is pH 6 – 8

Beyond optimal pH, reaction rate slows Too low (acidic) H+ ions interact with

amino acid side-chains and disrupt weak bonds of the tertiary structure of enzyme

Too high (basic) OH- ions interact with amino acid side-chains and disrupt weak bonds of the tertiary structure of enzyme

Cofactors Small non-protein molecules that are

required for proper enzyme catalysis Inorganic—Zn, Fe, Cu Coenzymes—vitamins

Effects of Substrate Concentration The higher the

[substrate], the faster the rate (up to a limit)

If [substrate] high enough, enzyme is saturated with substrate Reaction rate depends on

how fast the active site can convert substrate to product

When reaction is saturated with substrate, you can speed up reaction rate by adding more enzyme

Effects of Enzyme Inhibitors

Competitive inhibitors—chemicals that resemble an enzyme’s normal substrate and compete with it for the active site Blocks active site from

substrate If reversible, can be

overcome by increasing substrate concentration

Substrate

Active site

Enzyme

Competitiveinhibitor

Normal binding

Competitive inhibition

Noncompetitive inhibitor

Noncompetitive inhibition

A substrate canbind normally to the

active site of anenzyme.

A competitiveinhibitor mimics the

substrate, competingfor the active site.

A noncompetitiveinhibitor binds to the

enzyme away from theactive site, altering the

conformation of theenzyme so that its

active site no longerfunctions.

Substrate

Active site

Enzyme

Competitiveinhibitor

Normal binding

Competitive inhibition

Noncompetitive inhibitor

Noncompetitive inhibition

A substrate canbind normally to the

active site of anenzyme.

A competitiveinhibitor mimics the

substrate, competingfor the active site.

A noncompetitiveinhibitor binds to the

enzyme away from theactive site, altering the

conformation of theenzyme so that its

active site no longerfunctions.

Competitive Inhibitor

Effects of Enzyme Inhibitors

Noncompetitive inhibitors—chemicals that bind to another part (allosteric site)of an enzyme Causes enzyme to change

shape and prevents substrate from fitting in active site

Essential mechanism in cell’s regulating metabolic reactions

Substrate

Active site

Enzyme

Competitiveinhibitor

Normal binding

Competitive inhibition

Noncompetitive inhibitor

Noncompetitive inhibition

A substrate canbind normally to the

active site of anenzyme.

A competitiveinhibitor mimics the

substrate, competingfor the active site.

A noncompetitiveinhibitor binds to the

enzyme away from theactive site, altering the

conformation of theenzyme so that its

active site no longerfunctions.

Substrate

Active site

Enzyme

Competitiveinhibitor

Normal binding

Competitive inhibition

Noncompetitive inhibitor

Noncompetitive inhibition

A substrate canbind normally to the

active site of anenzyme.

A competitiveinhibitor mimics the

substrate, competingfor the active site.

A noncompetitiveinhibitor binds to the

enzyme away from theactive site, altering the

conformation of theenzyme so that its

active site no longerfunctions.

Allosteric site

Negative Feedback

Metabolic Control often Depends on Allosteric Regulation

Allosteric enzymes have 2 conformations, catalytically active and inactive

Binding of an activator to the allosteric site stabilizes active conformation

Binding of an inhibitor (noncompetitive) to the allosteric site stabilizes inactive conformation

Control of Metabolism

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

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)

Mitochondria,sites of cellular respiration

1 µm

Specific Localization of Enzymes Within the Cell

Structures within the cell help bring order to metabolic pathways

Some enzymes act as structural components of membranes

Some enzymes reside in specific organelles, such as enzymes for cellular respiration being located in mitochondria