Enzymes can be inhibited or poisoned by ligands binding to the active site or metal ion prosthetic groups. The addition of azide ions to the enzyme carbonic anhydrase inhibits its activity by binding more strongly to the zinc ion than the native water ligand. Heavy metal ions can also poison enzymes by replacing native metal ions or forming stable complexes with sulfur amino acids, altering the enzyme's confirmation and deactivating it. Thioneins protect against heavy metal poisoning by binding strongly to the metals through their sulfur groups.

1. INHIBITION AND
POISONING OF ENZYMES
CECH-612
UNIT-4(A)
by - Ms Mayuri Sompura

2. • Ligands can occupy an active site in an enzyme and can also
coordinate strongly to the metal ion of the prosthetic group of that
enzyme would naturally resist their detachment from the enzyme.
• Attachment of substrate with metal ion of that enzyme might inhibit
the action of that enzyme.
• Example:
if azide ion is added to enzyme carbonic anhydrase, it could
occupy in active site close to Zn+2 ion of the enzyme.
• The azide ion would coordinate with the Zn+2 ion replacing Zn←OH2
bond with a stronger Zn←azide bond.
• Consequently, the enzyme carbonic anhydrase would not get
converted into hydroxy form which is active form of catalyst for the
reversible hydration of carbon dioxide.
by - Ms Mayuri Sompura

3. • The addition of azide ion would inhibit the catalytic action of carbonic
anhydrase.
• Addition of small amounts of CN- and H2S would inhibit the
enzymatic activity of carbonic anhydrase.
• Sometimes heavier metal ions such as Cd+2, Hg-2, As+3 replace the
metal ion of prosthetic group of an enzyme.
• This deactivates the enzyme.
• Apart from this, the heavier metal ions (soft acids) form extremely
stable complexes with the S-containing amino acid units (soft bases)
of the epoenzyme.
by - Ms Mayuri Sompura

4. • This soft acid – base interaction brings about very significant changes
in the confirmation of the enzyme loses its activity as a catalyst.
• This is known as poisoning of catalyst.
• The poisoning effect of heavy metal ions can sometimes be reversed
by adding S- containing ligands such as cysteine, glutathione and 2,3
dimercaptopropanol to the biological system containing the poisoned
enzyme.
• These compound bind more strongly with the heavy metal ions than
the thio groups present in epoenzymes.
by - Ms Mayuri Sompura

5. Nature has devised its own mechanism of keeping away the heavy metal
ion poisoning.
• As soon as the metallo enzyme is under attack of heavy metal ions, the
concentration of thionenins ( a group of protein with high molar mass)
increases in liver, kidneys and spleen.
• The exact mechanism for direction of presence of the presence of the
heavy metal ion by the body and the reason for the production of
thionenins are not yet known.
by - Ms Mayuri Sompura

6. • These thioneins are built from 60 condensed amino acids, one third of
which are S-containing amino acid units having several free SH
group.
• These free SH groups have strong tendency to bind with heavy metal
ions (soft acid-base interactions).
• The thioneins therefore bind with the heavy metals ions more strongly
as compared to the enzymes and thus protect the metallo enzymes
from being poisoned by heavy ions.
by - Ms Mayuri Sompura

7. • Assignment :-
• Write a note on : inhibition and poisoning of enzymes
by - Ms Mayuri Sompura

8. Role of alkali and alkaline
earth metal ions in biological
systems
CECH-612
UNIT-4(A)
by - Ms Mayuri Sompura