Chapter 8Chapter 8

An Introduction to Metabolism

Fig. 8-1

I. Metabolism

• The totality of an organism’s chemical reactions

II. Metabolic Pathways

• Begins with a specific molecule and ends with a product

• Each step is catalyzed by a specific enzyme

Enzyme 1 Enzyme 2 Enzyme 3

DCBA

• Catabolic pathways: release energy, break down molecules

• Ex. Cellular respiration - breakdown of glucose with oxygen

• Anabolic pathways: consume energy, build complex molecules

• Ex. Synthesis of protein from amino acids

III. Forms of Energy (E)

• Energy = capacity to cause change

• Kinetic E = E from motion

• Heat (thermal E) = KE from random movement of atoms or molecules

• Potential E = E because of location or structure

• Chemical E = PE available for release in a reaction

• Energy can be converted from one form to another

Fig. 8-2

Climbing up converts the kineticenergy of muscle movementto potential energy.

A diver has less potentialenergy in the waterthan on the platform.

Diving convertspotential energy tokinetic energy.

A diver has more potentialenergy on the platformthan in the water.

IV. The Laws of Energy Transformation

• Thermodynamics = the study of energy transformations

• Closed system = isolated from surroundings

• Open system = energy and matter can be transferred between system and surroundings

• Organisms = open systems

A. The First Law of Thermodynamics

• Energy of the universe is constant:

– Energy can be transferred and transformed, but it cannot be created or destroyed

• Principle of conservation of energy

B. The Second Law of Thermodynamics

• During every energy transfer or transformation, some energy is unusable, and is lost as heat

– Every energy transfer or transformation increases the entropy (disorder) of the universe

Chemicalenergy

Heat CO2

H2O

V. Free-Energy Change, G

• Free energy = available energy to do work when temp and pressure are uniform

• Change in free energy (∆G) during a process is related to the change in enthalpy (change in total energy (∆H)), change in entropy (disorder (∆S)), and temp in Kelvin (T):

∆G = ∆H – T∆S

• Only processes with a negative ∆G are spontaneous and can be harnessed to do work

• Free Energy Bozeman

VI. Free Energy and Metabolism

• Exergonic reaction proceeds with a net release of free energy (ΔG < 0) and is spontaneous

• Endergonic reaction absorbs free energy from its surroundings (ΔG > 0) and is nonspontaneous

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

Progress of the reaction

A. Equilibrium and Metabolism

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

• Cells are not in equilibrium; they are open systems experiencing a constant flow of materials

Fig. 8-7a

(a) An isolated hydroelectric system

∆G < 0 ∆G = 0

Fig. 8-7b

(b) An open hydroelectric system

∆G < 0

Fig. 8-7c

(c) A multistep open hydroelectric system

∆G < 0

∆G < 0

∆G < 0

VIII. Structure and Hydrolysis of ATP

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

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

• ATP Overview - Bozeman

• Bonds between the phosphate groups can be broken by hydrolysis (releasing energy)

• This release of energy comes from the chemical change to a state of lower free energy, not from the phosphate bonds themselves

Fig. 8-9

Inorganic phosphate

Energy

Adenosine triphosphate (ATP)

Adenosine diphosphate (ADP)

P P

P P P

P ++

H2O

i

X. How ATP Performs Work

• ATP powers 3 types of cellular work (mechanical, transport, and chemical)

• Energy from the exergonic reaction of ATP hydrolysis can be used to drive an endergonic reaction (energy coupling)

• Overall, coupled reactions are exergonic

• ATP drives endergonic reactions by transferring a phosphate group to some other molecule (phosphorylation)

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

XI. The Regeneration of ATP

• ATP is regenerated by addition of a phosphate group to adenosine diphosphate (ADP)

• The energy comes from catabolic reactions in the cell

• The chemical PE temporarily stored in ATP drives most cellular work

Fig. 8-12

P iADP +

Energy fromcatabolism (exergonic,energy-releasingprocesses)

Energy for cellularwork (endergonic,energy-consumingprocesses)

ATP + H2O

XII. Activation Energy

• Initial E needed to start a chemical reaction is the free energy of activation, or activation energy (EA)

• Activation energy is often supplied from heat

Fig. 8-14

Progress of the reaction

Products

Reactants

∆G < O

Transition state

Fre

e en

erg

y EA

DC

BA

D

D

C

C

B

B

A

A

XIII. Enzymes Lower the EA

• Enzymes catalyze reactions by lowering the EA

• Enzymes do not affect the change in free energy (∆G); they hasten reactions that would occur eventually

Fig. 8-15

Progress of the reaction

Products

Reactants

∆G is unaffectedby enzyme

Course ofreactionwithoutenzyme

Fre

e en

erg

y

EA

withoutenzyme EA with

enzymeis lower

Course ofreactionwith enzyme

XIV. Substrate Specificity of Enzymes

• substrate = reactant that an enzyme acts on

• enzyme-substrate complex = enzyme binding to its substrate

• Active site = region on enzyme where the substrate binds

• Induced fit = brings chemical groups of active site into positions that enhance their ability to catalyze the reaction

• Enzyme Overview - Bozeman

Fig. 8-16

Substrate

Active site

Enzyme Enzyme-substratecomplex

(b)(a)

XV. Enzyme’s Active Site

• 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

XVI. Effects on Enzyme Activity

• An enzyme’s activity can be affected by

– Each enzyme has optimum Temp and pH

– Chemicals that influence the enzyme (cofactors and inhibitors)

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

A. Cofactors

• Nonprotein enzyme helpers

• May be inorganic (such as a metal in ionic form) or organic

• Coenzyme = organic cofactor (vitamins)

B. Enzyme Inhibitors

• Competitive inhibitors bind to active site of enzyme, competing w/ substrate

• Noncompetitive inhibitors bind to another part of enzyme, causing enzyme to change shape and making active site less effective

• Ex. toxins, poisons, pesticides, and antibiotics

Fig. 8-19

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

Noncompetitive inhibitor

Active siteCompetitive inhibitor

Substrate

Enzyme

XVII. Allosteric Regulation of Enzymes

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

• Occurs when a regulatory molecule binds to a protein at one site and affects the protein’s function at another site

A Allosteric Activation and Inhibition

• Most allosterically regulated enzymes are made from polypeptide subunits

• Each enzyme has active (activator stabilizes) and inactive (inhibitor stabilizes) forms

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)

• Cooperativity = form of allosteric regulation that can amplify enzyme activity

• Binding by a substrate to one active site stabilizes favorable conformational changes at all other subunits

Fig. 8-20b

(b) Cooperativity: another type of allosteric activation

Stabilized activeform

Substrate

Inactive form

B. Feedback Inhibition

• End product of a metabolic pathway shuts down the pathway

• Prevents cell from wasting chemical resources by making more product than needed

• Biochemical Pathway (no inhibition)

• Feedback Inhibition of Biochemical Pathways

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