Essential Knowledge 4.B.1: Interactions between
molecules affect their structure and function

Enzymes belong to
what class of
macrmolecule?
◦ proteins

How do enzymes work?
◦ They lower the activation
energy required to get a
reactions started
Biological Catalysts
Reduce Energy Barrier

Why is the shape of an
enzyme important?
◦ Enzymes work with specific
substrates
◦ Enzymes must be able to
bind to the substrate
◦ The substrate must be
complementary to the
surface properties (shape
and charge) of the active
site
◦ The substrate must fit into
the enzyme’s active site
The structure of an enzyme
determines its function.
Induced Fit of substrate +
enzyme = enzyme substrate
complex
1 Substrates enter active site.
2 Substrates are held
in active site by weak
interactions.
Substrates
Enzyme-substrate
complex
6 Active
site is
available
for two new
substrate
molecules.
3 Active site can
lower EA and speed
up a reaction.
Enzyme
5 Products are
released.
Products
4 Substrates are
converted to
products.

Enzyme Facts:
◦
◦
◦
◦
Enzymes are reusable
Enzymes are substrate specific
Enzymes lower the activation energy of a reaction
Enzymes change shape upon binding to the
substrate – thus holding the substrate in such a way
to favor breaking existing bonds and making new
ones – Induced Fit

Many enzymes require nonprotein helpers in
order to function
◦ Cofactors and coenzymes interact with enzymes to
cause structural changes that alter the activity rate
of the enzyme
◦ The enzyme may only become active when all the
appropriate cofactors or coenzymes are present
and bind to the appropriate sites on the enzyme

What is the difference between a cofactor and
a coenzyme?
◦ Cofactor – inorganic, such as the metal atoms zinc,
iron and copper in ionic form
◦ Coenzyme – organic molecule; many are vitamins

Other molecules and the environment in
which the enzyme acts can enhance or inhibit
enzyme activity.
◦ Environmental factors that may alter enzyme shape
(particularly the tertiary structure) thereby altering
enzyme function
 Temperature
 pH
 Salt concentration
Rate of reaction
Optimal temperature for
Optimal temperature for
typical human enzyme (37°C) enzyme of thermophilic
(heat-tolerant)
bacteria (77°C)
60
80
Temperature (°C)
(a) Optimal temperature for two enzymes
0
20
40
Rate of reaction
Optimal pH for pepsin
(stomach
enzyme)
0
5
pH
(b) Optimal pH for two enzymes
1
2
3
4
120
100
Optimal pH for trypsin
(intestinal
enzyme)
6
7
8
9
10


Molecules can bind reversibly or irreversibly to an
enzyme’s active site or an allosteric site –
changing the activity of the enzyme
Regulation of enzyme activity helps control
metabolism


Allosteric regulation – (allo refers to “other”) a
regulatory molecule binds to the enzyme at a site
other than the active site - can either speed up
(activator) or slow down (inhibitor) the reaction
Cooperativity – a substrate molecule binding to one
active site in a multi-subunit enzyme triggers a
shape change in all the subunits – increasing the
reaction
(a) Normal binding
(b) Competitive inhibition
(c) Noncompetitive
inhibition
Substrate
Active
site
Competitive
inhibitor
Enzyme
Noncompetitive
inhibitor
(b) Cooperativity: another type of allosteric activation
(a) Allosteric activators and inhibitors
Allosteric enzyme
with four subunits
Active site
(one of four)
Regulatory
site (one
of four)
Substrate
Activator
Inactive form
Stabilized active form
Active form
Oscillation
Nonfunctional
active site
Inactive form
Inhibitor
Stabilized inactive
form
Stabilized active
form

Feedback inhibition is a common mode of
metabolic control. An end product of a
metabolic pathway can bind to an enzyme at
the start of the pathway – changing the shape
of the enzyme thereby “inhibiting” the
reaction from taking place
Active site
available
Isoleucine
used up by
cell
Active site of
Feedback
enzyme 1 is
inhibition
no longer able
to catalyze the
conversion
of threonine to
intermediate A;
pathway is
switched off. Isoleucine
binds to
allosteric
site.
Initial
substrate
(threonine)
Threonine
in active site
Enzyme 1
(threonine
deaminase)
Intermediate A
Enzyme 2
Intermediate B
Enzyme 3
Intermediate C
Enzyme 4
Intermediate D
Enzyme 5
End product
(isoleucine)


The change in function of an enzyme can be
interpreted from data regarding the
concentrations of product or substrate as a
function of time.
These representations demonstrate the
relationship between an enzyme’s activity,
the disappearance of substrate, and/or
presence of a competitive inhibitor.

What could we measure?
◦ Disappearance of H202
◦ Production of H2O and/or production of O2
◦ Heat given off