The document discusses end point inhibition and negative feedback in metabolic pathways. It explains that the end product (F) of a metabolic pathway can control its own production rate through negative feedback inhibition. Specifically, when levels of the end product F rise, it binds to and inhibits the first enzyme (eA) in the pathway. This prevents further production of intermediates (B, C, D and E) and F. When F levels decrease, the inhibition is relieved and F production can rise again. It then provides phosphofructokinase and ATP as an example, where ATP binds allosterically to inhibit the enzyme and switch off the pathway when its levels are high.

1. End point inhibition
 The first step (controlled by eA) is often controlled by
the end product (F)
 Therefore negative feedback is possible
A B C D E F
 The end products are controlling their own rate of
production
 There is no build up of intermediates (B, C, D and E)
eFeDeCeA
eB
Inhibition
© 2008 Paul Billiet ODWS

2.  When the level of F decreases,the pathway
will not be blocked and the level of end
product F will rise.
This type of self regulating mechanism is called
negative feedback.

3. Example: Phosphofructokinase and ATP
Substrate: Fructose-6-phosphate
Reaction
fructose-6-phosphate + ATP → fructose-1,6-bisphosphate + ADP
phosphofructokinase
© 2008 Paul Billiet ODWS

4. The switch: Allosteric inhibition
Allosteric means “other site”
E
Active site
Allosteric
site
© 2008 Paul Billiet ODWS

5. Switching off
 These enzymes
have two receptor
sites
 One site fits the
substrate like other
enzymes
 The other site fits
an inhibitor
molecule
Inhibitor fits into
allosteric site
Substrate
cannot fit into
the active site
Inhibitor
molecule
© 2008 Paul Billiet ODWS

6. The allosteric site the enzyme “on-
off” switch
E
Active
site
Allosteric
site emptySubstrate
fits into
the active
site
The inhibitor
molecule is
absent
Conformational
change
Inhibitor fits
into allosteric
site
Substrate
cannot fit
into the
active site
Inhibitor
molecule
is present
E
© 2008 Paul Billiet ODWS

7. A change in shape
 When the inhibitor is present it fits into its site
and there is a conformational change in the
enzyme molecule
 The enzyme’s molecular shape changes
 The active site of the substrate changes
 The substrate cannot bind with the substrate
 So the end product acts as a molecular switch
that turns the enzyme on and off .
© 2008 Paul Billiet ODWS