The rate of enzyme reactions can be altered during cell
metabolism by a number of important methods:1. Proteolytic cleavage – enzymes may be kept in an
inactive form until needed and then activated by
removal of a short section.
2. Allosteric enzymes change their shape in the
presence of small charged ions . These ions, or
modulators, increase or decrease the enzymes affinity
for its substrate
3. Allosteric enzymes may be switched on or off by the
attachment or removal of phosphate groups. This is
known as covalent modification
4. Inhibitors slow the action of enzymes – see next
lesson
Inactive enzymes can be activated by a process called
Proteolytic cleavage.
Example
The pancreas secretes the inactive enzyme typsinogen into the
duodenum. This is so that protein digestion does not start in the
pancreas itself. An enzyme called enterokinase is secreted from
the lining of the duodenum which processes the trypsinogen into
its active form trypsin by cutting off part of the protein chain.
The trypsin is able to digest the protein in food but also triggers
the activation of more trypsinogen.
Allosteric Enzymes and Modulators
Small ions called modulators may bind to an allosteric
enzyme, changing its shape in the process and also its affinity
for its substrate.
The modulator, also called the regulator or effector, can
have a positive or negative effect on allosteric enzyme
activity.
· Positive modulators (activators) bind with an allosteric
site on the enzyme and stabilise the ACTIVE
conformation therefore speeding up the reaction rate
Negative modulators (inhibitors) bind to an allosteric site
that stabilises the INACTIVE conformation of the
molecule, therefore slowing the reaction rate
Examples of activators are:
Ca2+ needed by thrombokinase. This converts
globular prothrombin protein to fibrous thrombin
protein which helps blood to clot.
 Cl- needed by salivary amylase. This hydrolyses
starch to maltose during digestion.
Summary of features associated with allosteric enzyme activity
• Modulator molecules bind to a site on the enzyme which is
remote from the active site
• When a positive modulator binds, the enzyme shape is altered
and the active site forms
• When a negative modulator binds, the enzyme shape is altered
and the active site no longer forms
Another way of regulating enzyme activity is by covalent
modification. This is achieved by covalent binding of a
variety of chemical groups to the enzyme which changes
the shape of the enzyme.
Examples of covalent modification
Addition or removal of a phosphate group with its 2 negative charges
Kinase adds phosphate group to molecule while phosphatase
removes it.
It is reversible.
Some enzymes are activated by phosphorylation others are
inactivated.
Example:- Muscle tissue needs glucose (in the form of
glucose-1-phosphate) for energy. Glycogen is broken
down by glycogen phosphorylase. The enzyme first needs
to be activated by adding phosphate to a serine group using
a kinase enzyme.
When muscular activity slows down, a phosphatase acts on
the phosphorylase to remove the phosphate group and
inactivate the enzyme.
Covalent Modification (e.g. with the enzyme
glycogen phosphorylase)
Inactive form
of glycogen
phosphate
ACTIVE form
of glycogen
phosphate
Covalent Modification of Enzymes (2)
•Some enzymes are activated by phosphorylation
others are inactivated.