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Inhibition of enzyme activity Various substances interfere with the operation of enzymes. These substances are called inhibitors . Significance of enzyme inhibitor study: Enzyme inhibition serves as a major control mechanism in biological system .

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Inhibition of enzyme activity

Various substances interfere with the operation of enzymes. These substances are called inhibitors.

Significance of enzyme inhibitor study:

  • Enzyme inhibition serves as a major control mechanism in biological system .
  • Many drugs and toxic agents act by inhibiting the enzyme
  • In studying the mechanism of action
inhibition of enzyme activity
Inhibition of Enzyme Activity
  • Enzyme inhibitors are classified into 3 major classes:
  • 1)Competitive
  • 2) Non-competitive
  • 3) uncompetitive
1 competitive inhibition
1) Competitive inhibition

Thistype of inhibition occurs when the inhibitor closely resembles the substrate.

So, they compete for binding reversibly the active site.

  • This type of inhibition is reversed by increasing the substrate concentration.
  • Vmaxis not altered & Km is increased.
1 competitive inhibition2
1) Competitive inhibition
  • Vmax is not altered & Km is increased.

Examples of competitive inhibition

A-Sulfa drugs

Sulfa drugs inhibit folic acid synthesis by bacterial cells by competing with para amino benzoic acid which is essential for folic acid formation.

B- Folate analogues are used as antitumorse.g.Aminopterin & Methotrexate are analogues of folic acid and compete with it for dihydrofolatereductase needed for activation of folic acid into tetrahydro folic acid.

examples of competitive inhibition
Examples of competitive inhibition

c) Malonate competes with succinate for the active site of succinatedehyrogenase enzyme.

2 non competitive inhibition
2) Non-competitive inhibition
  • This type of inhibition occurs when the inhibitor and substrate bind at different sites on the enzyme.
  • The non-competitive inhibitor, therefore can bind either free enzyme or ES complex, preventing reaction from occurring.
  • Km is not altered & Vmax is decreased.
2 non competitive inhibition2
2) Non-competitive inhibition
  • Km is not altered & Vmax is decreased.

Non-competitive Inhibition

  • Reversible
  • Reversible inhibitor bind to the enzyme by non covalent interactions.
  • So it dissociatesrapidly from the enzyme.
  • e.g. Inhibition of iron-containing cytochromes enzymes (CAT, GPx) with CN
  • Irreversible
  • Irreversible inhibitor bind to the enzyme by covalent bonds.
  • So it dissociates slowly from the enzyme.
  • e.g.Inhibition of SH-containing enzymes by heavy metals as pb, Hg.
allosteric enzymes regulatory enzymes
Allosteric enzymes ( Regulatory enzymes)
  • These are enzymes whose catalytic activity is modulated by reversible non-covalent binding of a specific compound (effector, modulator, modifier) at a site on enzyme molecule other than the active site.
  • This site is known as allosteric or regulatory site.
  • They are usually found in multienzyme system.

Enzyme (a) is allosterically inhibited by the end product.


These bounded metabolites lead to conformational changes of the active site , causing an increase or decrease in activity.

  • Hence, effectors that inhibit enzyme activity are termed the negative effectors, whereas those increasing enzyme activity are positive effectors.

e.gAcetyl CoA carboxylase is the regulatory enzyme in de novo synthesis of fatty acids, it is inhibited by fatty acids & stimulated by citrate.

  • The presence of allosteric effector can alter the affinity of the enzyme to its substrate (Km) or modify its catalytic activity (Vmax), or both.
positive effectors
Positive effectors
  • Those that increase catalytic activity are known as positive effectors.
  • When the effector molecule binds to the allosteric site, it results in alteration of the active site that stimulates substrate binding and catalytic activity.
negative effectors
Negative effectors
  • Effectors that reduce or inhibit catalytic activity are negative effectors.
  • When the effector molecule binds to the allosteric site, it inhibits substrate binding and the enzyme is inactivated.
  • When the effector is detached from the allosteric site the enzyme is active.
general characters of allosteric enzymes
General characters of Allosteric Enzymes:
  • Oligomeric proteins, consisting of multiple subunits which are either similar or dissimilar.
  • They catalyze irreversible reactions (rate determining enzyme).
  • Allosteric enzyme show a sigmoidal curve when reaction velocity is plotted against substrate conc.
  • The allosteric and the catalytic sites are distinctly separated on the enzyme molecule.
feed back inhibition
Feed back inhibition
  • This is an example of allosteric inhibition in which the end product binds to the regulatory enzyme at the start of the pathway and decreases its activity.
  • Isoenzymes ( also known as isozymes ) are different forms of the same enzyme with the same catalytic activity ( they catalyze the same reaction ) but migrate at different rates in electrophoresis.
  • These enzymes display different kinetic parameters (i.e. different Km values), or different regulatory properties.
  • e.g. lactate dehydrogenase (LDH);creatine phosphokinase (CPK) .
lactate dehydrogenase ldh
Lactate dehydrogenase (LDH):
  • It is a tetrameric protein (with 4 subunits).
  • Two distinct units were found; one from the heart (H) and another from the muscles (M).
  • The subunits are conjugated in different ways to give 5 types.
lactate dehydrogenase ldh1
Lactate dehydrogenase (LDH):

Electrophoretic separation of serum LDH produces the following 5 isoforms:

  • LDH-1 (H4) is found primarily in heart muscle and RBCs.
  • LDH-2 (H3M) is concentrated in heart muscle and RBCs .
  • LDH-3 (H2M2) is of highest concentration in the brain, kidney.
  • LDH-4 (HM3) is of highest concentration in the kidney, placenta, and pancreas.
  • LDH-5 (M4) is highest in the liver and skeletal muscle.
  • N.B LDH-1 > LDH-2 ( normally LDH-2 > LDH-1) in myocardial infarction. LDH-5 is î îî in liver congestion.
lactate dehydrogenase ldh2
Lactate dehydrogenase (LDH):
  • H4 & M4 show a distinct difference in their kinetic properties.
  • The H4 functions in an aerobic environment, so in heart, H4 has a great Km (low affinity for pyruvate), and therefore H4 reduce pyruvate into lactate at very slow rate and preferentially oxidized pyruvate into CO2 & H2O in Kreb’s cycle.
  • Whereas the M4functions optimally in an anaerobic environment. So in sk.muscle, M4 has a small Km & rapidly reduce pyruvate into lactate.
clinical enzymology
Clinical Enzymology
  • The measurement of the serum levels of numerous enzymes has been shown to be of diagnostic significance.
  • This is because the presence of these enzymes in the serum indicates that tissue or cellular damage has occurred resulting in the release of intracellular components into the blood.
enzymes as a diagnostic agent of a disease

Plasma enzymes

Non Functional


Enzymes as a diagnostic agent of a disease
  • There are two types of plasma enzymes

Functional plasma enzymes

  • Are those found normally in high concentration in the blood and perform specific function there.
  • e.g. blood – clotting enzymes and lipoprotein lipase enzyme.

Non-functional plasma enzymes:

  • Are tissue enzymes that appear in plasma only in very low concentration under normal condition.

( they perform no physiological function in blood ).

  • Marked increase in their blood level indicates destruction or injury of the corresponding tissue .
  • Thus, they can be used for diagnosis of diseases.

Non-functional plasma enzymes: e.g.

• Alanine aminotransferase (ALT): ↑↑↑ in acute viral hepatitis.

• Aspartate aminotransferase (AST): ↑↑chronic liver diseases as well as heart diseases.

• Alkaline phosphatase (ALP): increased in obstructive jaundice and bone disorders.

• Acid phosphatase (ACP): elevated in prostate cancer.

• Lipase (LPS): elevated in acute pancreatitis.