Proteins that catalyst reactions and are

responsible for many of the metabolic processes

occurring in living organisms sustaining life.
 Chemical reactions need an initial input of
energy = THE ACTIVATION ENERGY
 During this part of the reaction the
molecules are said to be in a transition
state.
 Increasing the temperature make molecules
move faster
 Biological systems are very sensitive to
temperature changes.
 Enzymes can increase the rate of reactions
without increasing the temperature.
 They do this by lowering the activation
energy.
 They create a new reaction pathway “a short
cut”
 Enzyme controlled reactions proceed 108 to 1011 times
faster than corresponding non-enzymic reactions.
 Enzymes are proteins
 They have a globular shape
 A complex 3-D structuree

Human pancreatic amylase

 One part of an
enzyme, the active
site, is particularly
important
 The shape and the
chemical
environment inside
the active site
permits a chemical
reaction to proceed
more easily
 An additional non-
protein molecule
that is needed by
some enzymes to
help the reaction
 Tightly bound
cofactors are called
prosthetic groups
 Cofactors that are
bound and released
easily are called
coenzymes
 Many vitamins are
coenzymes
Nitrogenase enzyme with Fe, Mo and ADP cofactors
Jmol from a RCSB PDB file © 2007 Steve Cook
H.SCHINDELIN, C.KISKER, J.L.SCHLESSMAN, J.B.HOWARD, D.C.REES
STRUCTURE OF ADP X ALF4(-)-STABILIZED NITROGENASE COMPLEX AND ITS

IMPLICATIONS FOR SIGNAL TRANSDUCTION; NATURE 387:370 (1997)

 The substrate of an enzyme are the reactants
that are activated by the enzyme
 Enzymes are specific to their substrates
 The specificity is determined by the active
site
 Fit between the substrate and the active site of the
enzyme is exact
 Like a key fits into a lock very precisely
 The key is analogous to the enzyme and the
substrate analogous to the lock.
 Temporary structure called the enzyme-substrate
complex formed
 Products have a different shape from the substrate
 Once formed, they are released from the active site
 Leaving it free to become attached to another
substrate
S
E
E
E

Enzyme- Enzyme may

substrate be used again
complex P

Reaction coordinate
 This explains enzyme specificity
 This explains the loss of activity when
enzymes denature
 Some proteins can change their shape (conformation)

 When a substrate combines with an enzyme, it induces a

change in the enzyme’s conformation

 The active site is then moulded into a precise conformation

 Making the chemical environment suitable for the reaction

 The bonds of the substrate are stretched to make the reaction

easier (lowers activation energy)
 Hexokinase (a) without (b) with glucose substrate

 This explains the enzymes that can react

with a range of substrates of similar types
http://www.youtube.com/watch?v=vTQybDgweiE
 substrate concentration
 pH
 temperature
 inhibitors
 Reaction
velocity

Substrate concentration

 The increase in velocity is proportional to

the substrate concentration
 Vmax

Reaction
velocity

Substrate concentration

 Faster reaction but it reaches a saturation point

when all the enzyme molecules are occupied.
 If you alter the concentration of the enzyme then
Vmax will change too.
 Optimum pH values

Enzyme
activity Trypsin

Pepsin

1 3 5 7 9 11
pH
 Extreme pH levels will produce denaturation

 The structure of the enzyme is changed

 The active site is distorted and the substrate molecules will

no longer fit in it

 At pH values slightly different from the enzyme’s optimum

value, small changes in the charges of the enzyme and it’s
substrate molecules will occur

 This change in ionisation will affect the binding of the

substrate with the active site.
 Q10 (the temperature coefficient) = the
increase in reaction rate with a 10°C rise in
temperature.

 For chemical reactions the Q10 = 2 to 3

(the rate of the reaction doubles or triples
with every 10°C rise in temperature)

 Enzyme-controlled reactions follow this rule

as they are chemical reactions

 The optimum temperature for an enzyme

controlled reaction will be a balance
between the Q10 and denaturation.
 Q10 Denaturation
Enzyme
activity

0 10 20 30 40 50
Temperature / °C
 For most enzymes the optimum
temperature is about 30°C
 Many are a lot lower,
cold water fish will die at 30°C because their
enzymes denature
 A few bacteria have enzymes that can
withstand very high temperatures up to
100°C
 Most enzymes however are fully denatured
at 70°C
 Inhibitors are chemicals that reduce the rate
of enzymatic reactions.

 They are usually specific and they work at low

concentrations.

 They block the enzyme but they do not

usually destroy it.

 Many drugs and poisons are inhibitors of

enzymes in the nervous system.
 Irreversible inhibitors: Combine with the
functional groups of the amino acids in the
active site, irreversibly.
Examples: nerve gases and pesticides,
containing organophosphorus, combine with
serine residues in the enzyme acetylcholine
esterase.
 Reversible inhibitors: These can be washed
out of the solution of enzyme by dialysis.
There are two categories.
1. Competitive: These
compete with the
substrate molecules
for the active site. E+I EI

The inhibitor’s action is Enzyme inhibitor

proportional to its
Reversible
reaction complex
concentration.
Resembles the
substrate’s structure
closely.
Succinate Fumarate + 2H++ 2e-
Succinate dehydrogenase

CH2COOH COOH CHCOOH

CH2

CH2COOH CHCOOH
COOH
Malonate
2. Non-competitive: These are not influenced by
the concentration of the substrate. It inhibits
by binding irreversibly to the enzyme but not
at the active site.
Examples
 Cyanide combines with the Iron in the
enzymes cytochrome oxidase.
 Heavy metals, Ag or Hg, combine with –SH
groups.
These can be removed by using a chelating agent
such as EDTA.
 Negative feedback: end point or end product
inhibition
 Poisons snake bite, plant alkaloids and nerve
gases.
 Medicine antibiotics, sulphonamides,
sedatives and stimulants
METABOLISM
METABOLISM