Metabolism
Metabolism = Catabolism + Anabolism
• Catabolic pathways – release energy & break down molecules
• Anabolic pathways – require energy & build larger molecules
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 8-10
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 8-17
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)