This document summarizes a seminar on biotransformation. It introduces biotransformation as the process by which substances are transformed chemically within the body. It outlines the two phases of biotransformation - Phase I involves functionalization reactions like oxidation, reduction and hydrolysis. Phase II involves conjugation reactions like glucuronide conjugation, glycine conjugation, acetylation and methylation that increase water solubility. The importance of biotransformation is that it can activate prodrugs, deactivate toxins, or sometimes produce toxic metabolites, and can also help break down pollutants in the environment.

1. A SEMINAR ON
BIOTRANSFORMATION
(Pharmaceutical Chemistry)
Submitted by:-
Nidhi Maheshwari
M.Sc. (Applied
Chemistry)

2. CONTENTS
• INTRODUCTION
• CHEMICAL PATHWAY OF BIOTRANSFORMATION
• IMPORTANCE OF BIOTRANSFORMATION

3. INTRODUCTION
Biotransformation is the process by
which a substance is transformed from
one chemical to another by a chemical
reaction within the body.
Metabolism of drugs and toxins
(mainly for their effective removal) is
an important example of
biotransformation.

4. Chemical Pathways of
Biotransformation
BIOTRANSFORMATION
PHASE I
REACTIONS
OXIDATION
REDUCTION
HYDROLYSIS
PHASE II
REACTIONS
GLUCURONIDE
CONJUGATION
GLYCINE
CONJUGATION
ACETYLATION
METHYLATION
SULPHATION

5. PHASE I REACTIONS
These are ‘Functionalization Reactions or
Synthetic Reactions’.
Pharmacological role:
Water-solubility: ↑ (slightly faster excretion)
Biological activity: in general ↓
but often ↑

6. Oxidation
 Addition of Oxygen or negatively charged radical or
removal of Hydrogen or positively charged radical.
 Most common Phase I reaction and takes place in
liver.
 Enzymes: mainly Cytochrome P-450 (microsomal),
others are non-microsomal like Monoamine
Oxidase.
 Examples: Aliphatic Hydroxylation, Aromatic
Hydroxylation, N-Dealkylation, O-Dealkylation,
Deamination, N-Oxidation, S-Oxidation.

7.  N - Hydroxylation of Dapsone
 O - Dealkylation of Phenacetin

8. Reduction
Less common transformation.
Usually reversible reactions: true
reversible (catalysed by same enzyme in
both directions) or apparent reversible
(catalysed by different enzymes in both
directions).
Enzyme: Cytochrome P450.
Examples: Azo reduction,
dehalogenation, nitro reduction.

9. • Azo reduction of Prontosil to active
Sulphanilamide

10. Hydrolysis
Cleavage of xenobiotic in the presence of
water molecule.
Leads to large chemical changes as it
leads to loss of large fragments.
Enzymes: Cholinesterase and other
plasma esterases.

11. • Hydrolysis of Aspirin
• Hydrolysis of Penicillins

12. PHASE II REACTIONS
These are ‘Conjugation Reactions or
Synthetic Reactions’.
Pharmacological role:
Water-solubility: ↑ ↑ ↑ ↑ (rapid excretion)
Biological activity: almost always ↓
very seldom ↑

13. Glucuronide Conjugation
Most important Phase II transformation.
Substrate: Compounds with ―COOH
and ―OH group
Conjugating substrate: D - Glucuronic
acid
Enzyme: UDP - Glucuronyl transferase.

14.  Glucuronide conjugation of Chloramphenicol

15. Glycine Conjugation
Substrate: Compounds with ―COOH
group (usually aromatic substrate)
Conjugating substrate: Glycine
Enzymes: Acyl Coenzyme A synthetase
and Glycine N - acyltransferase.

16.  Glycine Conjugation of Salicylic Acid

17. Acetylation
Substrate: compounds having amino or
hydrazine residues.
Conjugating substrate: Acetyl
Coenzyme A
Enzyme: N - acetyl transferase.

18.  Acetylation of Isoniazid

19. Methylation
Substrate: Amines and Phenols
Conjugating substrate: Methyl donors
like Methionine and Cystein
Enzyme: Methyltransferase.

20.  Methylation of Histamine

21. Sulphation
Substrate: Phenolic compounds and
Steroids
Conjugating substrate: 3’-
phosphoadenosine - 5’- phosphosulphate
(PAPS)
Enzyme: Sulphotransferase

22.  Sulphation of Paracetamol

23. IMPORTANCE OF
BIOTRANSFORMATION
Formation of active metabolites in the body.
Transformation of drugs from: active to
inactive form (detoxification), active to
active metabolite, inactive (prodrug) to
active form or active to toxic form
(biotoxification).
Biotransformation of pollutants is
bioremedial for contaminated environment.

24. THANK
YOU