An Introduction to Metabolism

Metabolism

Metabolism = Catabolism + Anabolism

• Catabolic pathways – release energy & break down molecules

• Anabolic pathways – require energy & build larger molecules

LE 8-3

Chemical energy

Heat CO2

First law of thermodynamics Second law of thermodynamics

H2O

Energy

Free Energy

Free Energy (G) = energy available to perform work

G = H - T S

LE 8-5

Gravitational motion Diffusion Chemical reaction

LE 8-6a

Reactants

EnergyProducts

Progress of the reaction

Amount ofenergy

released(G < 0)

Fre

e en

erg

y

Exergonic reaction: energy released

LE 8-6b

ReactantsEnergy

Products

Progress of the reaction

Amount ofenergy

required(G > 0)

Fre

e en

erg

y

Endergonic reaction: energy required

LE 8-8

Phosphate groups

Ribose

Adenine

ATP

LE 8-10

Endergonic reaction: G is positive, reactionis not spontaneous

Exergonic reaction: G is negative, reactionis spontaneous

G = +3.4 kcal/mol

G = –7.3 kcal/mol

G = –3.9 kcal/mol

NH2

NH3Glu Glu

Glutamicacid

Coupled reactions: Overall G is negative;together, reactions are spontaneous

Ammonia Glutamine

ATP H2O ADP P i

+

+ +

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

+ +

+

LE 8-12

Pi

ADP

Energy for cellular work

(endergonic, energy-

consuming processes)

Energy from catabolism

(exergonic, energy-

yielding processes)

ATP

+

LE 8-14

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

LE 8-15

Course ofreactionwithoutenzyme

EA

without enzyme

G is unaffectedby enzyme

Progress of the reaction

Fre

e en

erg

y

EA withenzymeis lower

Course ofreactionwith enzyme

Reactants

Products

LE 8-16

Substrate

Active site

Enzyme Enzyme-substratecomplex

LE 8-17

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 the transition state,• providing a favorable microenvironment,• participating directly in the catalytic reaction.

Substrates areconverted intoproducts.

Products arereleased.

Activesite is

availablefor two new

substratemolecules.

LE 8-18a

Optimal temperature fortypical human enzyme

Optimal temperature forenzyme of thermophilic (heat-tolerant bacteria

Temperature (°C)

Optimal temperature for two enzymes

0 20 40 60 80 100

Rat

e o

f re

acti

on

LE 8-18b

Optimal pH for pepsin(stomach enzyme)

Optimal pHfor trypsin(intestinalenzyme)

pH

Optimal pH for two enzymes

0

Rat

e o

f re

acti

on

1 2 3 4 5 6 7 8 9 10

LE 8-19a

Substrate

Active site

Enzyme

Normal binding

A substrate canbind normally to the

active site of anenzyme.

LE 8-19b

Competitiveinhibitor

Competitive inhibition

A competitiveinhibitor mimics the

substrate, competingfor the active site.

LE 8-19c

Noncompetitive inhibitor

Noncompetitive inhibition

A noncompetitiveinhibitor binds to the

enzyme away from theactive site, altering the

conformation of theenzyme so that its

active site no longerfunctions.

LE 8-20a

Allosteric enzymewith four subunits

Regulatorysite (oneof four) Active form

Activator

Stabilized active form

Active site(one of four)

Allosteric activatorstabilizes active form.

Non-functionalactive site

Inactive formInhibitor

Stabilized inactive form

Allosteric inhibitorstabilizes inactive form.

Oscillation

Allosteric activators and inhibitors

LE 8-20b

Substrate

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

Cooperativity another type of allosteric activation

Stabilized active formInactive form

LE 8-UN141

Enzyme 1

A B

Reaction 1

Enzyme 2

C

Reaction 2

Enzyme 3

D

Reaction 3

ProductStarting

molecule

LE 8-21

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)