Biotransformation is the process by which substances are chemically altered within the body. It involves phase I and phase II reactions. Phase I reactions involve oxidation, reduction, and hydrolysis and make substances more polar. Phase II reactions conjugate substances with molecules like glucuronic acid, glycine, or sulfate, further increasing water solubility. Biotransformation is important as it can convert drugs to active or inactive metabolites, detoxify toxins, and help eliminate substances from the body. It also plays a role in synthesizing important metabolites and cleaning contaminated environments.

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BIOTRANSFORMATION
Introduction
Biotransformation is the process whereby a substance is
changed from one chemical to another, i.e., transformed by a
chemical reaction within a body.
Biotransformation means chemical alteration of chemicals
such as nutrients, amino acids, toxins and drugs (xenobiotics)
in the body.
Thus, metabolism of drugs or toxins in the body is also an
example of biotransformation. In other words,
biotransformation is a chemical mechanism of elimination of
xenobiotics.
Chemical Pathways of
Biotransformation
Biotransformation reactions are categorized by the normal
sequence with which they tend to react with a xenobiotic.
They are classified as follows:-
1. PHASE I REACTIONS
Also called Functionalization Reactions or Asynthetic
Reactions, during these a functional group is added to the
molecule at which conjugation can take place. Thus, by
way of these reactions, a polar group is either introduced or
unmasked, if already present on the otherwise lipid soluble

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substrate. For example, ―OH, ―COOH, ―NH2, ―SH,
etc.
The chemical reactions that take place during phase I
biotransformations are:-
A. Oxidation
B. Reduction
C. Hydrolysis
A. Oxidation: Oxidative reactions are the most common
type of Phase I biotransformation reactions. These
involve addition of oxygen or negatively charged
radical or removal of hydrogen or positively charged
radical.
These reactions increase the hydrophilicity of
xenobiotics and are usually catalysed by non-specific
enzymes located in microsomes (mainly Cytochrome
P450) and non-microsomal enzyme like Monoamino
oxidase.
Common oxidative reactions are aliphatic
hydroxylation, aromatic hydroxylation, N-
dealkylation, O- dealkylation, deamination, N-
oxidation and S- oxidation. Some examples are:
 N- Hydroxylation of Dapsone

3.  O- dealkylation of Phenacetin
B. Reduction: These are less common reactions and are
also catalysed by Cytochrome
reversible reactions and may be catalysed by same
enzyme (true reversible reaction
enzymes (apparent reversible reaction).
Some common reduction reactions are azo reduction,
dehalogenation, nitro reduction, etc.
For example,
 Azo reduction of Prontosil
C. Hydrolysis: It is the cleavage of xenobiotic molecule
by taking up a molecule of water in the presence of
enzymes like cholinesterase and other plasma esterases.
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dealkylation of Phenacetin
These are less common reactions and are
also catalysed by Cytochrome P450. These are usually
reversible reactions and may be catalysed by same
true reversible reaction) or by different
enzymes (apparent reversible reaction).
Some common reduction reactions are azo reduction,
dehalogenation, nitro reduction, etc.
Azo reduction of Prontosil
It is the cleavage of xenobiotic molecule
by taking up a molecule of water in the presence of
enzymes like cholinesterase and other plasma esterases.
These are less common reactions and are
P450. These are usually
reversible reactions and may be catalysed by same
or by different
Some common reduction reactions are azo reduction,
It is the cleavage of xenobiotic molecule
by taking up a molecule of water in the presence of
enzymes like cholinesterase and other plasma esterases.

4. This reaction results in a large chemical change
substrate brought about by loss of relatively large
fragment of molecules.
Some examples are
 Hydrolysis of Aspirin
 Hydrolysis of Penicillins
Phase I reactions generally produce a more water soluble
and less active compound but sometimes it also leads to
production of an active metabolite (active drug from
prodrug) or toxic metabolite.
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This reaction results in a large chemical change
substrate brought about by loss of relatively large
fragment of molecules.
Some examples are
Hydrolysis of Aspirin
Hydrolysis of Penicillins
Phase I reactions generally produce a more water soluble
and less active compound but sometimes it also leads to
production of an active metabolite (active drug from
prodrug) or toxic metabolite.
This reaction results in a large chemical change in
substrate brought about by loss of relatively large
Phase I reactions generally produce a more water soluble
and less active compound but sometimes it also leads to
production of an active metabolite (active drug from

5. 2. PHASE II REACTIONS
Also called Conjugation reaction or
during these, a suitable moiety is conjugated to the
molecule at a pre
functional group acquired in phase I reactions.
The main chemical reactions that take place during Phase
II biotransformations ar
A. Glucuronide Conjugation
B. Glycine Conjugation
C. Acetylation
D. Methylation
E. Sulphation
A. Glucuronide Conjugation:
Acid Conjugation, it is the most important phase II
reaction. The conjugating moiety in this reaction is D
Gucuronic acid (derived from D
reaction takes place in the presence of enzyme UDP
glucuronyl transferase. Compounds with ―OH and
―COOH groups undergo this type of conjugation.
For example,
 Glucuronide conjugation of chloramphenicol
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PHASE II REACTIONS
Also called Conjugation reaction or Synthetic Reaction
during these, a suitable moiety is conjugated to the
molecule at a pre - existing functional group or at a
functional group acquired in phase I reactions.
The main chemical reactions that take place during Phase
II biotransformations are:-
Glucuronide Conjugation
Glycine Conjugation
Glucuronide Conjugation: Also called Glucuronic
Acid Conjugation, it is the most important phase II
reaction. The conjugating moiety in this reaction is D
acid (derived from D – glucose)
reaction takes place in the presence of enzyme UDP
glucuronyl transferase. Compounds with ―OH and
―COOH groups undergo this type of conjugation.
Glucuronide conjugation of chloramphenicol
Synthetic Reaction;
during these, a suitable moiety is conjugated to the
existing functional group or at a
The main chemical reactions that take place during Phase
Also called Glucuronic
Acid Conjugation, it is the most important phase II
reaction. The conjugating moiety in this reaction is D –
glucose). The
reaction takes place in the presence of enzyme UDP –
glucuronyl transferase. Compounds with ―OH and
―COOH groups undergo this type of conjugation.
Glucuronide conjugation of chloramphenicol

6. B. Glycine Conjugation:
reaction is Glycine (an amino acid), which reacts with
―COOH group containing substrate (usually aromatic
substrate) in the presence of enzyme Acetyl Coenzyme
A synthetase and Glycine N
For example,
 Glycine conjugation of
C. Acetylation: Compounds having amino or hydrazine
residues are conjugated with the help of Acetyl
Coenzyme A in the presence of enzyme
transferase.
For example,
 Acetylation of Isoniazid
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Conjugation: The conjugation moiety in this
reaction is Glycine (an amino acid), which reacts with
―COOH group containing substrate (usually aromatic
substrate) in the presence of enzyme Acetyl Coenzyme
A synthetase and Glycine N – acyltransferase.
Glycine conjugation of Aspirin
Compounds having amino or hydrazine
residues are conjugated with the help of Acetyl
Coenzyme A in the presence of enzyme N
Acetylation of Isoniazid
The conjugation moiety in this
reaction is Glycine (an amino acid), which reacts with
―COOH group containing substrate (usually aromatic
substrate) in the presence of enzyme Acetyl Coenzyme
Compounds having amino or hydrazine
residues are conjugated with the help of Acetyl
N – acetyl

7. D. Methylation: The amines and phenols are methylated
by methyl donors like methionine and cystein in the
presence of enzyme methyltransferase.
For example,
 Methylation of histamine
E. Sulphation: The phenolic compounds and steroids are
sulphated by sulphotransferase
phosphoadenosine
For example,
 Sulphation of paracetamol
These increase the water solubility of the substrate to a
great extent and thus they can be easily eliminated from the
body.
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The amines and phenols are methylated
by methyl donors like methionine and cystein in the
presence of enzyme methyltransferase.
Methylation of histamine
The phenolic compounds and steroids are
sulphated by sulphotransferase. The cosubstrate is 3’
phosphoadenosine – 5’ – phosphosulphate (PAPS).
Sulphation of paracetamol
These increase the water solubility of the substrate to a
great extent and thus they can be easily eliminated from the
The amines and phenols are methylated
by methyl donors like methionine and cystein in the
The phenolic compounds and steroids are
. The cosubstrate is 3’ –
phosphosulphate (PAPS).
These increase the water solubility of the substrate to a
great extent and thus they can be easily eliminated from the

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Importance of biotransformation
Biotransformations are the important metabolic chemical
reactions that take place in the body of living being.
 These are important in synthesis of many important and
active metabolites.
 Drugs undergo potential biotransformations in the body;
which leads to conversion of active drugs to inactive
metabolites (detoxification), active drug to active
metabolite, inactive drug (prodrug) to active drug, active
drug to toxic metabolite (biotoxification).
 Biotransformation of various pollutants is a sustainable
way to clean up contaminated environment.
References:-
1. Essentials of Pharmacotherapeutics; F.S.K. Barar.
2. Medicinal Chemistry – Principles and Practice; Edited by
F.D. King.
3. Biopharmaceutics and Pharmacokinetics – A Treatise;
D.M. Brahmankar, Sunil B. Jaiswal.
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