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
Starting Product
molecule
 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 spontaneous
Reactants

Amount of
energy
released
Free energy

(∆G <0)
Energy
Products

5.2 Progress of the reaction

 Reactions in Metabolism
 An endergonic reaction
 Is one that absorbs free energy from its
surroundings and is not spontaneous
Products

Amount of
energy
Free energy

released
(∆G>0)
Energy
Reactants

5.2
Progress of the reaction
ATP hydrolysis
 Can be coupled to other reactions

Endergonic reaction: ∆G is positive, reaction

is not spontaneous
NH2

+ NH3 ∆G = +3.4 kcal/mol

Glu Glu
Glutamic Ammonia Glutamine
acid

Exergonic reaction: ∆ G is negative, reaction

is spontaneous

ATP + H2O ADP + P ∆G = - 7.3 kcal/mol

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
 The three types of cellular work are powered by the
hydrolysis of ATP P i
P

Motor protein Protein moved

(a) Mechanical work: ATP phosphorylates motor proteins
Membrane
protein ADP
ATP +
P i
P P i

Solute Solute transported

(b) Transport work: ATP phosphorylates transport proteins

P NH2
Glu + NH3 + P i
Glu
Reactants: Glutamic acid Product (glutamine)
and ammonia made
(c) Chemical work: ATP phosphorylates key reactants
 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 Energy
 Is the initial amount of energy needed to start a
chemical reaction
A B

C D
Transition state

A B EA
Exergonic
Free energy

C D
Reaction
Reactants
A B
∆G < O
C D

Products
Progress of the reaction
5.4
 The effect of enzymes on activation
energy and reaction rate
Course of
reaction EA
without without
enzyme enzyme
EA with
enzyme
is lower
Reactants
Free energy

Course of ∆G is unaffected
reaction by enzyme
with enzyme

Products

Progress of the reaction

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
Substrate
 Is the region on the
enzyme where the
substrate binds
 The active site is Active site
designed to fit to a
specific substrate

Enzyme

5.5
 Induced Fit Model
 Induced fit binding enzyme
of a substrate
 Brings chemical groups
of the active site into substrate
positions that allow
them to catalyze the
chemical reaction with
the substrate

Enzyme- substrate
complex

5.6
 Induced Fit Model
1 Substrates enter active site; enzyme
changes shape so its active site 2 Substrates held in
embraces the substrates (induced fit). active site by weak
interactions, such as
hydrogen bonds and
ionic bonds.

3 The active site (R groups of

Substrates its amino acids) can lower
Enzyme-substrate
EA and speed up a reaction
complex
by:

6 Active site 3. orienting substrates

Is available for correctly
two new 4. straining substrate bonds
substrate 5. providing a favorable
Mole. microenvironment
Enzyme 6. covalently bonding to the
substrate

5 Products are
Released. 4 Substrates are
5.6/5.7 Products Converted into
Products.
 Effects of Temperature
 Each enzyme has an optimal temperature in which it
can function
Optimal temperature for Optimal temperature for
typical human enzyme enzyme of thermophilic (heat-tolerant)
bacteria
Rate of reaction

0 20 40 80 100
Temperature (Cº)

5.8
Effects of pH
 Each enzyme has an optimal pH in which it can
function
Optimal pH for pepsin Optimal pH
(stomach enzyme) for trypsin
(intestinal
enzyme)
Rate of reaction

0 1 2 3 4 5 6 7 8 9
pH

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 A substrate can
bind normally to the Substrate

inhibitors active site of an

enzyme. Active site
 Bind to the
active site of an Enzyme
enzyme and
compete with the Normal binding
substrate A competitive
inhibitor mimics the Competitive
substrate, competing inhibitor
for the active site.

Competitive inhibition
5.8
 Enzyme Inhibitors
 Noncompetitive
inhibitors
 Bind to another
part of an
A noncompetitive
enzyme causing inhibitor binds to the
enzyme away from
a change in the the active site, altering
shape of the the conformation of
the enzyme so that its
active site active site no longer
functions.

Noncompetitive inhibitor

5.8 Noncompetitive inhibition

 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
Allosteric activator
stabilizes active form
 Many enzymes Allosteric enzyme
with four subunits Active site
change shape
when regulatory
molecules bind Regulatory
to specific sites, site
Activator
Active form Stabilized active form
affecting
function Allosteric activator
stabilizes active form

Non-functional
active site

Inhibitor
Inactive form Stabilized inactive
5.9 form
 Allosteric Regulation
 Cooperativity Binding of one substrate molecule to
active site of one subunit locks
 Is a form of all subunits in active conformation.
allosteric
regulation that
can amplify Substrate

enzyme activity

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
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

5.9