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• Questions to be answered during this lecture

• A- What are isoenzymes?
• B- What are the clinical implications of
• C- What are enzymes’ inhibitors and what are
their types?
• D- What are the factors that regulate enzymes’
• There are two types of enzymes in plasma:
• 1- Functional plasma enzymes:

A- are synthesized mostly in liver

B- present in blood in equivalent or higher
concentrations than tissues
C- they have biological functions in blood
D- They are found mainly in the form of
proenzymes which are inactive precursors of
enzymes which are activated by specific proteases
(ex: blood clotting factors)

E- their substrates are found in plasma

• 2-Non-functional plasma enzymes:

• A- they have no physiological function in blood

• B- their substrates are absent from blood

• C- they are absent from plasma or found in very small

• D- their presence in blood in high concentration
suggests an increased rate of tissue destruction.

• E- their presence in high level in blood provide

the physicians with valuable diagnostic and
prognostic information regarding the type of
tissue that was exposed to injury.
• Example of isoenzymes are creatine kinase (CK) enzyme ,
this enzyme is found in three forms:

• 1- BB: this form is found in the brain

• 2- BM: this form is found in heart
• 3- MM: this form is found mainly in skeletal muscles

• The three forms catalyze the same biochemical reaction

but they have different chemical and physical properties.
Clinical implications of
• Because Creatine kinase (CK) is A non-functional
plasma enzyme, so it must be absent from plasma and
its presence in high concentration indicates the
presence of some sort of tissue injury.

• When a patient presented to hospital with suspected

myocardial infarction we investigate for the
isoenzyme found in the heart which is MB, so
isoenzymes impose an important diagnostic tool for
diseases by which we can locate the source of tissue
3-Enzyme inhibition
Different chemical agents (metabolites, substrate
analogs, toxins, drugs, metal complexes etc) can
inhibit the enzyme activity.
Inhibitor (I) binds to an enzyme and prevents the
formation of ES complex or breakdown it to E + P
Reversible inhibitors
• Competitive inhibitors increase Km by
lowering the affinity of the enzyme to its

• Non-competitive inhibitors affect Vmax

leading to decrease in reaction velocity.
4-Regulation of enzyme’s
Methods of regulation of enzyme activity

• 1- Regulation of enzyme synthesis at the level of

• 2-Allosteric regulation
• 3-Covalent modification
2-Allosteric regulation
Allosteric enzymes have a second
regulatory site (allosteric site) distinct
from the active site

Allosteric enzymes contain more than one

polypeptide chain (have quaternary

Allosteric modulators bind noncovalently to

allosteric site and regulate enzyme activity
via conformational changes
2 types of modulators (inhibitors or
Negative modulator (inhibitor)
–binds to the allosteric site and inhibits the action of the enzyme
–usually it is the end product of a biosynthetic pathway - end-product
(feedback) inhibition

• Positive modulator (activator)

–binds to the allosteric site and stimulates activity
–usually it is the substrate of the reaction
3- Covalent modifications
There are two types of covalent modifications:
A- Partial proteolysis
B- Phosphorylation

A- Phosphorylation:
Enzymes are activated or inhibited by adding or removing a
phosphoryl group

B- Partial proteolysis:
Some enzymes are produced in inactive form called (zymogen) and
then activated by proteases.
Activation by proteolytic cleavage

Many enzymes are synthesized as inactive precursors

(zymogens) that are activated by proteolytic cleavage
• Proteolytic activation only occurs once in the life of an
enzyme molecule
Examples of specific proteolysis
•Digestive enzymes
–Synthesized as zymogens in stomach and pancreas

•Blood clotting enzymes

–Cascade of proteolytic activations

•Protein hormones
–Proinsulin to insulin by removal of a peptide