Lesson 2
 Repro


Enzyme question
Slides 17-22
 Jot
down the key ideas from last lesson on to
some scrap/spare paper.
 What
were some of the key words and
phrases?
 Use
them in a sentence/paragraph to
describe what enzymes do...
Some enzymes need the help of...

Some enzymes can only work if another small, non-protein
molecule is attached to them (non permanent).
enzyme
active site
substrate
cofactor
The presence of cofactors such as certain ions may help the
formation of the enzyme-substrate complex.
 Some cofactors are free and can even join with the substrate to
make the correct, complementary shape required (co-substrates).
 Some cofactors change the charge distribution on the surface of
the substrate or enzyme and make the temporary bonds in the
ES-complex easier to form.
e.g. Amylase will only digest starch in the presence of chloride ions

 Carbonic
anhydrase with zinc ion
permanently bound to its active site.
 Found in red blood cells
 Catalyses conversion of carbon dioxide
and water to carbonic acid, which
then breaks down into protons and
hydrogencarbonate ions.
 Important for the removal of CO2 from
respiring tissues to the lungs


Along with cofactors and prosthetic groups,
coenzymes are another small molecule that helps
the enzyme-substrate complex form.
Coenzymes bind temporarily to the active site of enzymes.
Unlike prosthetic groups
and other cofactors,
coenzymes are changed
in a reaction.
What’s
need tothe
be implication
recycled or need a
source
of
this?of more
Many vitamins act as coenzymes.
 Vitamin C is a very important coenzyme.


Nicotinamide (NAD) is a very important coenzyme
needed by cells. The RDA for humans is 18mg.
The amount of NAD used in metabolic reactions is a
great deal more than 18mg. Suggest why the RDA is
so low.
The NAD is constantly recycled, which means that
there is a always a supply of it. Therefore not much
is needed in the diet.
 Have
a similar shape to that of the substrate
molecule
 Complementary shape to the active site
 Inhibitor occupies the active site, forming enzymeinhibitor complexes.
 Does not lead to the formation of products
 Most do not bind permanently


They bind for a short period of time and then leave.
Their action is described as reversible, as the removal
of the inhibitor form the reaction mixture leaves the
enzyme molecule unaffected.
•
•
The level of inhibition depends on the concentrations
of inhibitor and substrate.
As the number of substrate molecules is increased,
the level of inhibition decreases because a substrate
molecule is more likely than an inhibitor molecule to
collide with the active site.
 Does
not compete with substrate molecules
for a place in the active site.
 Instead, they attach to the enzyme,
molecule in a region away from the active
site.




This distorts the tertiary structure of the
enzyme molecule, leading to the shape of the
active site changing.
This means that the substrate no longer fits
into the active site
Enzyme-substrate complexes cannot form
The reaction rate decreases.
 Most
non-competitive inhibitors bind
permanently to the enzyme molecule. The
inhibition is irreversible



The level of inhibition depends on the number of
inhibitor molecules present.
If there are enough inhibitor molecules to bind to all of
the enzyme molecules present, then the enzyme
controlled reaction will stop.
Changing the substrate concentration will have no effect
Example 1: Snake Venom
Inhibitor name: A protein called
fasciculation is found in snake venom.
Function: Inhibits Acetylcholinesterase
which is an enzyme used to degrade a
neurotransmitter called Acetylcholine
(Serotinin is another example of a
neurotransmitter that you should have
heard of from GCSE).
How: Fasciculation acts as a competitive
inhibitor preventing the acetylcholine from
being broken down by Acetylcholinesterase
after an impulse transmission.
Effect: In skeletal muscle fasciculations
stop nerve impulses from being transmitted
and hence stop muscle contraction.
Eventually this will lead to flaccid
Normal (no
venom)
After venom
Example 2: Cyanide poisoning
Inhibitor name: Potassium cyanide
Function: Inhibits a vital respiratory enzyme called cytochrome oxidase (found
inside mitochondria)
How: Cytochrome oxidase normally combines oxygen and hydrogen together to
form water and allows ATP creation.
Cyanide non competitively
inhibits chytochrome oxidase
changing the shape of its active
site meaning no ATP creation.
Effect: Any reactions requiring
ATP are no longer supplied. The
body eventually has no energy
supply causing total cell failure
… and death even though all
products for respiration still
present.
Example 1: HIV Protease inhibitors
Inhibitor name: Protease inhibitors (many
variations all under research)
Function: Competitively inhibits HIV virus
protease enzymes. Normally the virus uses
this to cut viral RNA into smaller pieces so
as into implant genes into the host cells DNA
and hence replicate).
How: The inhibitor binds specifically with
the HIV protease enzymes active site
preventing longer viral RNA pieces from
bindings, as a result the RNA is not cut into
smaller pieces so it cannot be implanted
into the host cells DNA = no replication.
Effect: A host cell can be infected by HIV
but it cannot be ‘hijacked’ into making
more HIV copies as a result of DNA
Normal
(no
inhibitor)
With
protease
inhibitor
(red)
Example 1: Suspected antifreeze
poisoning treatment
Inhibitor name: Ethanol (alcohol!)
Function: Ethylene glycol is found in
antifreeze, if ingested can be broken
down by alcohol dehydrogenase (liver)
forming extremely toxic oxalic acid =
death. Ethanol if taken as a treatment
can prevent this.
How: Ethanol competitively inhibits
alcohol dehydrogenase so give the patient
a massive dose of ethanol so as to prevent
ethylene glycol from interacting with
alcohol dehydrogenase.
Effect: Less oxalic acid is produced
allowing the harmless ethylene glycol to
be excreted. Better to be drunk than
Broken down
by alcohol
dehydrogenase
into Oxalic
acid
Ethylene
glycol
Massive
ethanol
dosage
Ethanol
(inhibitor)
Ethylene glycol excreted
 Product
of an enzyme binds to the enzymes
and inhibits its action
 Way to regulate metabolism
 Form of negative feedback

E.g. regulation of ATP formation by
phosphofructokinase (an enzyme in
glycolysis)

ATP inhibits phosphofructokinase, so that when
ATP levels are high, glucose is not broken down
 Some
enzymes produced in inactive
precursor form
 E.g. Trypsin produced in the small intestine
as Trypsinogen
 After they’re made some amino acids are
removed by another enzyme


Thus completing the shape/or exposing the
active site
E.g. trypsinogen turned into trypsin

Discuss with a partner:
The difference between intracellular and
extracellular enzymes, and examples of each.
The similarities and differences between:
Cofactors, Prosthetic Groups and Coenzymes.
The role of enzymes in catalysing both
intracellular and extracellular reactions
 To include catalase as an example of an enzyme
that catalyses intracellular reactions and
amylase and trypsin as examples of enzymes that
catalyse extracellular reactions.
The need for coenzymes, cofactors and prosthetic
groups in some enzyme-controlled reactions
 To include Cl – as a cofactor for amylase, Zn2+ as
a prosthetic group for carbonic anhydrase and
vitamins as a source of coenzymes.