Regulation of Enzyme Activity


For an organism to respond to changing conditions and cellular needs,

very sensitive controls over enzyme activity are required.


Three mechanisms of regulation of enzyme activity:

1. Activation of Zymogens


Some enzymes are manufactured by the body in inactive form.

In order to make them active,

a small part of their polypeptide chain must be removed.


zymogen or proenzyme - the inactive precursor of an enzyme

- must be activated by removing a small portion

of the polypeptide chain.


For example: Trypsin is an important enzyme for the digestion of the

proteins that we eat. It cleaves protein in the small intestine.


Trypsinogen, the inactive form of trypsin, is synthesized

in the pancreas.


Only after it has entered the small intestine is it activated by

the hydrolysis of a single peptide bond.


trypsinogen + H2O ----------------- trypsin + hexapeptide


We would not want it active before it entered the small intestine,

because it would hydrolyze the proteins our bodies are made of.












feedback inhibition - a process in which the end product of a sequence of

enzyme-catalyzed reactions inhibits an earlier step in the process.


Enzymes are often regulated by environmental conditions.

The reaction product of one enzyme may control the activity of another.


E1 E2 E3

For example: A ------> B ------> C ------> D


The last product in the chain, D, may inhibit the activity of enzyme E1.

Thus when the concentration of D is low, the three reactions proceed rapidly.

But as the concentration of D increases, the action of E1 becomes inhibited

and eventually stops.

In this way the synthesis of D is stopped,

when the cell has enough D for its present needs.


2. Allosteric Regulation

Allosteric regulation involves the combination of the enzyme with some

other compound such that the three-dimensional conformation

of the enzyme is altered and its catalytic activity is changed.


modulator - a compound that binds to the enzyme at a location other than

the active site and alters the catalytic activity.

- may be an activator or inhibitor

activator - a substance that binds to a allosteric enzyme and

increases its activity

- a noncompetitive inhibitor is the other kind of modulator


allosteric enzyme - an enzyme with a quaternary structure

whose activity is changed by the binding of modulators.

- have two binding sites

- one for the substrate (the active site)

- one for the modulator (regulator)

- binding of the modulator changes the overall 3-D shape

of the enzyme, including the structure of the active site.




Example: the five step synthesis of the amino acid isoleucine (see fig. 10-13)


Threonine deaminase, the enzyme that catalyzes the first step in the

first step in the conversion of threonine to isoleucine, is subject to

inhibition by the final product, isoleucine.


The structures of isoleucine and threonine are quite different,

so isoleucine is not a competitive inhibitor, but a noncompetitive

inhibitor (or modulator)


Also, the site to which isoleucine binds to the enzyme is different

from the enzyme active site that binds to threonine.


This type of allosteric regulation is an example of feedback inhibition.


























3. Genetic Control


The synthesis of all proteins, including enzymes, is under genetic control by

nucleic acids.

Genetic control of enzyme activity involves enzyme induction.


enzyme induction - the synthesis of an enzyme in response

to a temporary need of the cell.


For example: E. coli bacteria use b-galactosidase to catalyze the hydrolysis

of b-lactose to b-D-galactose and b-D-glucose



b-lactose + H2O ----------------------> b-D-galactose + b-D-glucose


When E. coli bacteria are in a medium that contains no b-lactose,

the number of b-galactosidase molescules per cell of E. coli

is less than ten.


However, if E. coli bacteria are added to a medium that contains b-lactose,

the bacterium begins to produce thousands of molecules of

b-galactosidase within minutes.