Enzyme Cofactor

Cofactors are non-protein chemical compounds that are

associated with enzymes. A cofactor acts as a catalyst and
regulates the functioning of an enzyme. An enzyme without a
cofactor is called an apoenzyme. An enzyme and its cofactor
together constitute the holoenzyme.
Three Kinds of Cofactors Present in Enzymes:

Prosthetic groups: These are cofactors covalently or permanently bound

to an enzyme at all times. A FAD (Flavin Adenine Dinucleotide) is a
prosthetic group present in many enzymes.

Coenzyme: A coenzyme is an organic, non-protein compound that binds

to an enzyme only during catalysis. At all other times, it is detached from
the enzyme. NAD+ is a common coenzyme.

Metal ions: For the catalysis of certain enzymes, a metal ion is required
at the active site to form coordinate bonds. Zn2+ is a metal ion cofactor
used by a number of enzymes.
Daniel Koshland suggested the induced fit model in 1958. This is one of
the main models, describing the enzyme-substrate interaction.
According to the hypothesis, the active site of the enzyme does not
have a rigid conformation.

Therefore, the substrate does not completely fit into the active site of
the enzyme. Hence, the enzyme’s active site modifies its shape upon
the binding of the substrate, becoming complementary to the shape of
the substrate. Significantly, this conformational change is possible due
to the flexibility of the protein.
Lock and Key Mechanism: The lock and key model was
suggested by Emil Fischer in 1894 and is hence known as
Fisher’s theory and it describes the enzyme-substrate
interaction.

The lock and key model suggested by Emil Fischer in 1894.

Therefore, it is also known as Fisher’s theory. This is the second
model, which describes the enzyme-substrate interaction.
According to the lock and key model, the active site of the enzymes serves
as the ‘lock’ while its substrate serves as the ‘key’. On that basis, the shape
of the active site of the enzyme is complementary to the shape of the
substrate. Thereby, the active site of the enzyme can hold the substrate
closer to the enzyme by forming an unusable intermediate compound,
which is the enzyme-substrate complex.
Mechanism of Enzyme Action
An enzyme’s active site attracts substrates towards it, catalyses the chemical
reaction by which products are formed. After product formation, allows the
products to dissociate or separate from the enzyme’s surface. The combination
formed by an enzyme and its substrates is called the enzyme-substrate complex.

EEnzyme+SSubstrate⇁↼[ES]Enzyme–SubstrateComplex→EEnzyme+Pproduct

Collision of any two molecules along with the right orientation and a satisfactory
amount of energy is needed for the reaction to occur. This energy between these
molecules needs to overcome the barrier in the reaction, which is known as
Activation Energy. The substrate and the enzyme form an intermediate reaction
with low activation energy without any catalysts.
(i) Competitive inhibition
In competitive inhibition, there is close resemblance in the
structure of inhibitor I and substrate S, therefore, they
both compete for the same active site on the enzyme. The
enzyme can form enzyme-substrate ES complex or it can
form enzyme-inhibitor EI complex but not both
ESI.
(iii) Uncompetitive inhibition
In this type of inhibition, inhibitor does not bind to free
enzyme. It binds only to enzyme substrate (ES) complex
directly or its binding is facilitated by the conformational
change that takes place after substrate binds to enzyme
Allosteric enzymes

Allosteric enzymes do not obey MichaelisMenten kinetics. These enzymes in

general consist of more than one protein subunits, therefore, more than one
active sites are present.

Allosteric enzymes result in sigmoidal graph instead of rectangular hyperbola

when v0 is plotted against substrate concentration [S].

Each subunit of allosteric enzymes also contain regulatory site along with active
site.

Regulatory molecules may reversibly bind to the regulatory site and

alter the affinity of enzyme for substrate binding.