Regulation of enzyme activity

Mechanisms of regulating enzyme activity

1. Allosteric enzymes
• Enzymes whose activity can be changed by
molecules (effector molecules) other than
substrate.
• Allosteric means other site or other structure.
• The interaction of an inhibitor at an allosteric
site changes the structure of the enzyme so
that the active site is also changed.
Processes involving the allosteric enzyme
i. Negative allosterism
Effector binding sites alters the shape of the active site of the enzyme making
it to an inactive configuration

ii. Positive allosterism

Effector binding sites that alters the shape of inactive site of enzyme to an
active configuration. Therefore binding of the effector molecule regulates
enzyme activity by determining whether it will be active or not.
2. Feedback inhibition
• An enzyme regulation process in which formation of a product inhibits an
earlier reaction in the sequence. It controls the allosteric enzymes.
• This occurs when an end product of a pathway accumulates as the
metabolic demand for it declines.
• This end product in turn binds to the regulatory enzyme at the start of the
pathway and decreases its activity the greater the end product levels the
greater the inhibition of enzyme activity.
3. Proenzymes (Zymogen)
• The inactive form of enzyme which can be activated by removing
a small part on their polypeptide chain.
• Mostly are digestive enzymes and blood clotting enzymes
4. Protein Modification
• Another mechanism that can on and off the enzyme.
• This is a process in which a chemical group is covalently
added to or removed from the protein.
• The most common example is phosphorylation in which a
phosphate is transferred from an activated donor (usually
ATP) to an amino acid on the regulatory enzyme.
 Enzyme Inhibitors

Non specific Specific

Denaturation Irreversible Reversible

Competitive Non competitive

Acids and bases Allosteric
Temperature feedback
Alcohol
Heavy metals
Reducing agents
Enzyme Inhibitors
Enzyme inhibitors are chemical that can bind to enzyme and either
eliminate or drastically reduce their catalytic ability
Classification
1.Reversibility
Deals whether the inhibition will eventually dissociate from the enzyme
releasing it in the active form.
2. Competition
Refers whether the inhibitor is a structural analog or look alike of the
substrate. If so the inhibitor and substrate will compete for the enzyme’s
active site
Enzyme inhibitors
1. Irreversible inhibitors
2. Reversible inhibitors
a. Competitive inhibitors
b. Uncompetitive inhibitors
c. Mixed inhibitors
d. Non competitive inhibitors
Irreversible inhibitors
• Usually covalently modify an enzyme and inhibition can therefore not be
reversed.
• Often contains highly reactive functional group such as aldehydes, alkenes ,
haloalkenes etc
Reversible inhibitors
• Bind to enzymes with non covalent interactions such as hydrogen bonds,
hydrophobic interactions and ionic bonds.
• Generally don not undergo chemical reactions when bound to the enzyme
and can be easily removed.
Competitive inhibitor
• They are molecules that resemble the structure and charge distribution of the
natural substrate for a particular enzyme.
• The inhibition is competitive because the inhibitor and substrate compete for
the binding to the enzymes active site.
Uncompetitive inhibition
The inhibitor binds only to the substrate–enzyme complex.
Mixed inhibition
• The inhibitor can bind to the enzyme at the same time as the enzymes
substrate. However the binding of the inhibitor affects the binding of
the substrata and vice versa.
• Although it is possible for mixed type inhibitors to bind in the active
site, this type of inhibition generally results from an allosteric effect
where the inhibitor binds to a different site on an enzyme.
Non competitive inhibitor
• Is a form of mixed inhibitor where the binding of the inhibitor to the
enzyme reduces its activity but does not affect the binding of substrate.
• Binds to R groups of amino acids or perhaps to the metal ion cofactor.
• Modifies the shape of the active site.