enzymes and metabolism
TRANSCRIPT
Advanced Biology
Enzymes and Metabolism
Metabolism Is the sum of an organism’s chemical
reactions Metabolic pathways begin with a specific
molecule and end with a product Each step is catalyzed by a specific enzyme
Enzyme 1 Enzyme 2 Enzyme 3
A B C D
Reaction 1 Reaction 2 Reaction 3
Startingmolecule
Product
Metabolism
Catabolic pathways Break down complex molecules into
simpler compounds Release energy
Anabolic pathways Build complicated molecules from simpler
ones Consume energy
5.1
Free Energy
Energy that is free to do work in cells (∆G)
Organisms are continually expending free energy
How is it replaced?
Where is it stored?
5.2
Reactions in Metabolism
An exergonic reaction Proceeds with a net release of free energy and
is spontaneousReactants
Products
Energy
Progress of the reaction
Amount ofenergyreleased (∆G <0)
Fre
e e
ner
gy
5.2
Reactions in Metabolism
An endergonic reaction Is one that absorbs free energy from its
surroundings and is not spontaneous
Energy
Products
Amount ofenergyreleased (∆G>0)
Reactants
Progress of the reaction
Fre
e e
ner
gy
5.2
ATP hydrolysis Can be coupled to other reactions
Endergonic reaction: ∆G is positive, reaction is not spontaneous
∆G = +3.4 kcal/molGlu Glu
∆G = - 7.3 kcal/molATP H2O+
+ NH3
ADP +
NH2
Glutamicacid
Ammonia Glutamine
Exergonic reaction: ∆ G is negative, reaction is spontaneous
P
Coupled reactions: Overall ∆G is negative; together, reactions are spontaneous ∆G = –3.9 kcal/mol
How ATP Performs Work
ATP drives endergonic reactions By phosphorylation, transferring a
phosphate to other molecules
How ATP Performs Work
(c) Chemical work: ATP phosphorylates key reactants
P
Membraneprotein
Motor protein
P i
Protein moved(a) Mechanical work: ATP phosphorylates motor proteins
ATP
(b) Transport work: ATP phosphorylates transport proteinsSolute
P P i
transportedSolute
GluGlu
NH3
NH2P i
P i
+ +
Reactants: Glutamic acid and ammonia
Product (glutamine)made
ADP+
P
The three types of cellular work are powered by the hydrolysis of ATP
Enzymes
A catalyst Is a chemical agent that speeds up a
reaction without being consumed by the reaction
An enzyme Is a protein catalyst Enzymes speed up metabolic reactions
by lowering activation energy
5.3
Activation EnergyF
ree
ener
gy
Progress of the reaction
∆G < O
EAA B
C D
Reactants
A
C D
B
Transition state
A B
C D
Products
Is the initial amount of energy needed to start a chemical reaction
Exergonic Reaction
5.4
The effect of enzymes on activation energy and reaction rate
Progress of the reaction
Products
Course of reaction without enzyme
Reactants
Course of reaction with enzyme
EA
withoutenzyme
EA with enzymeis lower
∆G is unaffected by enzymeF
ree
ener
gy
5.4
Substrate Specificity of Enzymes
The substrate Is the reactant an enzyme acts on
The enzyme Binds to its substrate, forming an
enzyme-substrate complex
5.5
Enzyme Specificity The active site
Is the region on the enzyme where the substrate binds
The active site is designed to fit to a specific substrate
Substrate
Active site
Enzyme
5.5
Induced Fit Model Induced fit binding
of a substrate Brings chemical groups
of the active site into positions that allow them to catalyze the chemical reaction with the substrate
Enzyme- substratecomplex
substrate
enzyme
5.6
Induced Fit Model
Substrates
Products
Enzyme
Enzyme-substratecomplex
1 Substrates enter active site; enzymechanges shape so its active siteembraces the substrates (induced fit).
2 Substrates held inactive site by weakinteractions, such ashydrogen bonds andionic bonds.
3 The active site (R groups of its amino acids) can lower EA and speed up a reaction by:
1. orienting substrates correctly
2. straining substrate bonds3. providing a favorable
microenvironment4. covalently bonding to the
substrate
4 Substrates are Converted intoProducts.
5 Products areReleased.
6 Active siteIs available fortwo new
substrateMole.
5.6/5.7
Effects of Temperature Each enzyme has an optimal temperature in which it
can functionOptimal temperature for
enzyme of thermophilic (heat-tolerant) bacteria
Rat
e o
f re
acti
on
0 20 40 80 100Temperature (Cº)
Optimal temperature fortypical human enzyme
5.8
Effects of pH Each enzyme has an optimal pH in which it can
function
Rat
e o
f re
acti
on
pH
Optimal pH for pepsin (stomach enzyme)
Optimal pHfor trypsin(intestinalenzyme)
10 2 3 4 5 6 7 8 9
5.8
Cofactors
Cofactors Are nonprotein enzyme helpers such as
the metals iron, zinc and copper Coenzymes
Are organic cofactors and include most vitamins
5.8
Enzyme Inhibitors
Competitive inhibitors Bind to the
active site of an enzyme and compete with the substrate
Competitive inhibition
A competitiveinhibitor mimics the
substrate, competingfor the active site.
Competitiveinhibitor
A substrate canbind normally to the
active site of anenzyme.
Substrate
Active site
Enzyme
Normal binding
5.8
Enzyme Inhibitors
Noncompetitive inhibitors Bind to another
part of an enzyme causing a change in the shape of the active site
A noncompetitiveinhibitor binds to the
enzyme away fromthe active site, altering
the conformation ofthe enzyme so that its
active site no longerfunctions.
Noncompetitive inhibitor
Noncompetitive inhibition5.8
Enzyme Regulation
Regulation of enzyme activity helps control metabolism
Allosteric enzyme regulation Is the term used to describe any case in which a
protein’s function at one site is affected by binding of a regulatory molecule at another site
5.9
Allosteric Regulation Many enzymes
change shape when regulatory molecules bind to specific sites, affecting function
Non-functional active site
Stabilized inactiveform
Allosteric activatorstabilizes active formAllosteric enzyme
with four subunits Active site
Regulatorysite
Active formActivator
Stabilized active form
Allosteric activatorstabilizes active form
InhibitorInactive form5.9
Allosteric Regulation
Cooperativity Is a form of
allosteric regulation that can amplify enzyme activity
Binding of one substrate molecule toactive site of one subunit locks all subunits in active conformation.
Substrate
Inactive form Stabilized active form
5.9
Feedback Inhibition
In feedback inhibition The end product of a metabolic pathway
shuts down the pathway
5.9
Feedback inhibition
5.9
The end product binds to the enzyme inhibiting its ability to catalyze the reaction with the initial substrate
This is very common in metabolic pathways as a form of regulation