BCH421 – Xenobiotics

5 Xenobiotic Biotransformation - Phase I Reactions

Lecture outline
5 Xenobiotic Biotransformation - Phase I Reactions .............................................................. 1
Lecture outline...................................................................................................................................... 1
Introduction .......................................................................................................................................... 2
Lecture learning outcomes (LLOs)...................................................................................................... 2
5.1 Xenobiotic Biotransformation - Phase I Reactions ................................................................. 3
5.2 Types of Phase I Reactions ....................................................................................................... 3
5.2.1 Oxidation Reactions .................................................................................................... 3
5.2.2 Reduction Reactions .................................................................................................... 5
5.2.3 Hydrolysis Reactions .................................................................................................... 6
5.2.4 Dealkylation Reactions ................................................................................................ 7
5.2.5 Dehalogenation Reactions ......................................................................................... 9
5.2.6 Epoxidation Reactions............................................................................................... 10
5.2.7 N-Oxidation Reactions .............................................................................................. 11
5.2.8 S-Oxidation Reactions ............................................................................................... 13
5.3 Examples of Phase I Reactions in Drug Metabolism ........................................................... 14
5.4 Importance of Phase I Reactions ........................................................................................... 14

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Introduction
In the intricate landscape of biochemical processes within living organisms, xenobiotic
biotransformation stands as a critical mechanism, orchestrating the transformation of
foreign substances, or xenobiotics, into metabolites that are more amenable to elimination.
This complex and highly regulated series of enzymatic reactions plays a pivotal role in
ensuring the body's defense against potentially harmful compounds, whether they be
environmental toxins, drugs, or other exogenous substances.

At the forefront of xenobiotic biotransformation are Phase I reactions, the initial metabolic
transformations that set the stage for subsequent processes. These reactions are
characterized by their ability to introduce or expose functional groups on xenobiotics,
rendering them more reactive and facilitating further modifications in Phase II reactions.

The primary objective of Phase I reactions is to increase the water solubility of xenobiotics,
as hydrophilic compounds are generally more easily excreted from the body. These
reactions typically involve the modification of chemical structures through oxidation,
reduction, hydrolysis, or other transformative processes. One of the key enzyme families
responsible for orchestrating these reactions is the cytochrome P450 superfamily, whose
members exhibit remarkable substrate specificity and contribute significantly to the
diversity of Phase I reactions.

Understanding Phase I reactions is integral to comprehending the fate of xenobiotics within

an organism. It not only influences the pharmacokinetics of drugs but also shapes the
body's response to environmental exposures. Moreover, the intricate balance between
activation and detoxification within Phase I reactions underscores the delicate nature of
xenobiotic biotransformation.

In this exploration of Phase I reactions, we will delve into the diverse mechanisms employed
by the body to metabolize and neutralize foreign compounds. From oxidation to reduction,
each reaction type contributes uniquely to the dynamic process of xenobiotic
biotransformation, ultimately ensuring the maintenance of homeostasis and safeguarding
the organism from potential threats.

Lecture learning outcomes (LLOs)

By the end of this week, you should be able to
LLO 1. Define xenobiotic biotransformation.
LLO 2. Outline the significance of xenobiotic biotransformation.
LLO 3. Describe the phase I reactions as the initial step in xenobiotic
biotransformation.
LLO 4. State the significance of phase I reactions.
LLO 5. Describe different types of phase I reactions.
LLO 6. Examine examples of phase I reactions in drug metabolism.

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LLO 7. Evaluate the importance of phase I reactions.

LLO 8. Describe how phase I reactions play a crucial role in drug development,
therapeutic interventions, and the assessment of potential toxic effects.

5.1 Xenobiotic Biotransformation - Phase I Reactions

Xenobiotic biotransformation refers to the metabolic processes that modify and transform
foreign substances, often termed xenobiotics, within an organism. These processes are
crucial for the elimination of potentially harmful compounds and play a key role in drug
metabolism, environmental toxin processing, and the body's response to various
substances. Phase I reactions represent the initial step in xenobiotic biotransformation,
involving chemical modifications that make the compounds more amenable to further
processing and excretion.

5.2 Types of Phase I Reactions

5.2.1 Oxidation Reactions

Oxidation reactions within xenobiotic biotransformation represent a crucial category of
metabolic processes where foreign substances undergo chemical modifications, often
mediated by enzymes such as Cytochrome P450 (CYP450). This class of reactions involves
the introduction of oxygen atoms into the substrate, typically resulting in the addition of
hydroxyl groups. The significance of oxidation reactions extends across various aspects of
drug metabolism, environmental detoxification, and the body's response to xenobiotics.

Cytochrome P450 enzymes, a diverse superfamily of heme-containing monooxygenases,

play a prominent role in mediating oxidation reactions. These enzymes are found in the
endoplasmic reticulum of cells, particularly in the liver, and exhibit remarkable substrate
specificity, contributing to the diverse range of xenobiotics they can metabolize.

Cytochrome P450 Enzymes: This family of enzymes, particularly CYP450, plays a

significant role in the oxidation of xenobiotics. These reactions involve the addition of
oxygen atoms to the substrate, often introducing hydroxyl groups.

Examples of Oxidation Reactions:

1. Hydroxylation of Aliphatic or Aromatic Hydrocarbons

Catalyst: Cytochrome P450 Enzymes

Outcome: Introduction of a hydroxyl group to the substrate.

Example: Hydroxylation of aliphatic or aromatic hydrocarbons, as observed in the

metabolism of drugs like diazepam. The added hydroxyl group enhances the water
solubility of the compound, facilitating its excretion.

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2. Epoxidation of Polycyclic Aromatic Hydrocarbons

Catalyst: Cytochrome P450 Enzymes

Outcome: Formation of epoxides, highly reactive compounds.

Example: Epoxidation of benzo[a]pyrene, a polycyclic aromatic hydrocarbon. The resulting

epoxides can further undergo detoxification or lead to the formation of reactive
intermediates.

3. N-Oxidation of Aromatic Amines

Catalyst: Cytochrome P450 Enzymes

Outcome: Introduction of oxygen to nitrogen atoms.

Example: N-oxidation of aromatic amines, such as diphenylamine. This modification

increases the water solubility of the substrate, aiding in its elimination.

Mechanism of Oxidation Reactions

The mechanism of oxidation reactions typically involves the following steps:

Substrate Binding: The xenobiotic substrate binds to the active site of the Cytochrome
P450 enzyme.

Oxygen Activation: Molecular oxygen (O2) is activated within the enzyme's active site,
resulting in the formation of a reactive oxygen species.

Hydroxylation: The activated oxygen species reacts with the substrate, introducing a
hydroxyl group through the transfer of an oxygen atom.

Product Formation: The hydroxylated product is released from the enzyme, now
possessing increased water solubility and often exhibiting altered pharmacological
properties.

Significance in Drug Metabolism

Oxidation reactions, particularly those mediated by Cytochrome P450 enzymes, play a

crucial role in drug metabolism. They can activate prodrugs, enhance elimination, or modify
the pharmacokinetics of drugs, influencing their therapeutic effects and potential side
effects.

Challenges and Considerations

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Despite their essential role, oxidation reactions can also lead to the formation of reactive
intermediates, which, in excessive amounts, may contribute to toxicity. Understanding the
balance between beneficial and adverse effects is crucial in evaluating the overall impact
of oxidation reactions in xenobiotic biotransformation

5.2.2 Reduction Reactions

Reduction reactions within xenobiotic biotransformation are integral processes involving
the addition of electrons to substrates, leading to a decrease in their oxidation state. These
reactions play a significant role in the metabolic transformation of foreign substances,
contributing to detoxification and elimination. Cytochrome P450 Reductase is a key enzyme
system that facilitates reduction reactions by donating electrons to cytochrome P450
enzymes.

Role of Cytochrome P450 Reductase

Cytochrome P450 Reductase is an electron-transferring enzyme located in the endoplasmic
reticulum of cells, particularly in the liver. It serves as a crucial partner to cytochrome P450
enzymes in the reduction of xenobiotics. The enzyme contains flavin mononucleotide (FMN)
and flavin adenine dinucleotide (FAD) cofactors, allowing it to transfer electrons to
cytochrome P450 enzymes during the reduction process.

Examples of Reduction Reactions

1. Reduction of Nitro Groups

Catalyst: Cytochrome P450 Reductase

Outcome: Addition of electrons to nitro groups, converting them to amino groups.

Example: Reduction of nitro groups in compounds like nitrofurantoin. This metabolic

transformation contributes to the detoxification of certain drugs.

Mechanism of Reduction Reactions

The mechanism of reduction reactions involves the transfer of electrons from cytochrome
P450 Reductase to cytochrome P450 enzymes, which, in turn, transfer these electrons to
xenobiotic substrates. In the context of reduction reactions, this process results in the
addition of electrons to specific functional groups, modifying the chemical structure of the
substrate.

Significance in Detoxification
Reduction reactions are crucial in detoxifying xenobiotics by converting reactive and
potentially harmful functional groups, such as nitro groups, into less reactive and more
readily excretable forms. This process enhances the water solubility of the substrate,
facilitating its elimination from the body.

Challenges and Considerations

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While reduction reactions are generally associated with detoxification, it's essential to note
that the process can also yield reactive intermediates. Therefore, understanding the
balance between beneficial detoxification and potential toxic outcomes is vital for assessing
the overall impact of reduction reactions in xenobiotic biotransformation.

Integration with Phase I Reactions

Reduction reactions with Cytochrome P450 Reductase are part of the broader landscape of
Phase I reactions. They complement oxidation reactions, collectively contributing to the
diverse array of transformations that xenobiotics undergo during their initial processing
within the body.

5.2.3 Hydrolysis Reactions

Hydrolysis reactions in xenobiotic biotransformation involve the cleavage of chemical
bonds through the addition of water molecules. Esterases and amidases are enzymatic
catalysts that play a crucial role in facilitating hydrolysis reactions. These reactions
contribute significantly to the metabolic processing of xenobiotics, particularly those
containing ester or amide functional groups.

Role of Esterases and Amidases

1. Esterases
• Esterases are enzymes that catalyze the hydrolysis of ester bonds.
• Found in various tissues, including the liver and gastrointestinal tract.
• Play a key role in the metabolism of ester-containing drugs and xenobiotics.

2. Amidases
• Amidases catalyze the hydrolysis of amide bonds.
• Present in different cellular compartments, including the cytoplasm and
mitochondria.
• Participate in the metabolism of amide-containing xenobiotics.

Examples of Hydrolysis Reactions

1. Hydrolysis of Ester Bonds:

• Catalyst: Esterases
• Outcome: Cleavage of ester bonds into a carboxylic acid and an alcohol.
• Example: Hydrolysis of procaine, a local anesthetic, by esterases.

2. Hydrolysis of Amide Bonds

• Catalyst: Amidases
• Outcome: Cleavage of amide bonds into a carboxylic acid and an amine.

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• Example: Hydrolysis of drugs containing amide groups, such as certain antibiotics.

Mechanism of Hydrolysis Reactions

1. Ester Hydrolysis
• Esterases catalyze the cleavage of ester bonds.
• The ester substrate reacts with water, resulting in the formation of a carboxylic acid
and an alcohol.
• The enzyme facilitates the transfer of a proton to the departing alcohol group.

2. Amide Hydrolysis
• Amidases catalyze the cleavage of amide bonds.
• The amide substrate reacts with water, leading to the formation of a carboxylic acid
and an amine.
• The enzyme facilitates the transfer of a proton to the departing amine group.

Significance in Detoxification
Hydrolysis reactions, particularly those involving ester and amide bonds, are crucial for
detoxifying xenobiotics by breaking down these functional groups. The resulting products
are often more water-soluble and can be readily excreted from the body.

Integration with Phase I Reactions

Hydrolysis reactions are an essential part of Phase I reactions, complementing oxidation
and reduction processes. They contribute to the overall diversity of transformations that
xenobiotics undergo during their initial metabolic processing.

Challenges and Considerations

While hydrolysis reactions are generally associated with detoxification, the activity of
esterases and amidases can also lead to the formation of potentially reactive metabolites.
Therefore, understanding the balance between beneficial detoxification and potential toxic
outcomes is vital for evaluating the overall impact of hydrolysis reactions in xenobiotic
biotransformation.

5.2.4 Dealkylation Reactions

Dealkylation reactions are a class of metabolic transformations within xenobiotic
biotransformation, involving the removal of alkyl groups from a substrate. Oxidative
dealkylation is a specific type of dealkylation reaction that employs oxidative processes to
cleave alkyl groups from xenobiotics. This reaction is often catalyzed by enzymes within the
cytochrome P450 family.

Role of Oxidative Dealkylation

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Oxidative dealkylation serves as a critical mechanism for the modification and metabolism
of xenobiotics, leading to alterations in their chemical structures. This process is particularly
relevant in the detoxification and elimination of drugs and environmental compounds
containing alkyl groups.

Examples of Oxidative Dealkylation

1. Demethylation of Methyl Groups:

• Catalyst: Cytochrome P450 Enzymes
• Outcome: Removal of a methyl group through oxidation.
• Example: Demethylation of caffeine to form theobromine. This reaction contributes
to the metabolism of methylxanthines and their subsequent elimination.

Mechanism of Oxidative Dealkylation

1. Substrate Binding
The xenobiotic substrate, containing an alkyl group, binds to the active site of a cytochrome
P450 enzyme.

2. Oxygen Activation
Molecular oxygen (O2) is activated within the enzyme's active site, leading to the formation
of a reactive oxygen species.

3. Dealkylation
The activated oxygen species reacts with the alkyl group, resulting in the cleavage of the
alkyl bond and the removal of the alkyl group from the substrate.

4. Product Formation
The dealkylated product, now modified and often more water-soluble, is released from the
enzyme.

Significance in Detoxification
Oxidative dealkylation plays a crucial role in the detoxification of xenobiotics by converting
alkylated compounds into more polar and water-soluble metabolites. This modification
enhances the excretion of the substrate from the body.

Integration with Phase I Reactions

Oxidative dealkylation is an integral part of Phase I reactions, contributing to the overall
diversity of transformations that xenobiotics undergo during their initial metabolic
processing. It often occurs alongside other oxidative reactions mediated by cytochrome
P450 enzymes.

Challenges and Considerations

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While oxidative dealkylation is generally associated with detoxification, the formation of

reactive intermediates during this process can pose challenges. Understanding the balance
between beneficial detoxification and potential toxic outcomes is crucial for evaluating the
overall impact of oxidative dealkylation reactions in xenobiotic biotransformation.

5.2.5 Dehalogenation Reactions

Dehalogenation reactions in xenobiotic biotransformation involve the removal of halogen
atoms from a substrate. This process is crucial for the metabolism and detoxification of
halogenated compounds, such as certain drugs and environmental pollutants.
Dehalogenation reactions are often mediated by enzymes within the cytochrome P450
family.

Role of Cytochrome P450 Enzymes in Dehalogenation

Cytochrome P450 enzymes, known for their diverse catalytic activities, play a significant role
in dehalogenation reactions. These enzymes can cleave carbon-halogen bonds, leading to
the removal of halogen substituents from xenobiotics.

Examples of Dehalogenation Reactions

1. Dehalogenation of Halothane
• Catalyst: Cytochrome P450 Enzymes
• Outcome: Removal of halogen atoms from halothane, a volatile anesthetic.
• Significance: This dehalogenation reaction contributes to the metabolism and
elimination of halothane from the body.

Mechanism of Dehalogenation Reactions

1. Substrate Binding
The halogenated substrate binds to the active site of a cytochrome P450 enzyme.

2. Oxygen Activation
Molecular oxygen (O2) is activated within the enzyme's active site, leading to the formation
of a reactive oxygen species.

3. Dehalogenation
The activated oxygen species reacts with the carbon-halogen bond, resulting in the
cleavage of the bond and the removal of the halogen substituent.

4. Product Formation
The dehalogenated product, now modified and often more water-soluble, is released from
the enzyme.

Significance in Detoxification

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Dehalogenation reactions are crucial for the detoxification of halogenated xenobiotics. By

removing halogen substituents, these reactions enhance the water solubility of the
substrate, facilitating its excretion from the body.

Integration with Phase I Reactions

Dehalogenation is an integral part of Phase I reactions, contributing to the overall diversity
of transformations that xenobiotics undergo during their initial metabolic processing. It
often occurs alongside other oxidative reactions mediated by cytochrome P450 enzymes.

Challenges and Considerations

While dehalogenation reactions are generally associated with detoxification, the formation
of reactive intermediates during this process can pose challenges. Understanding the
balance between beneficial detoxification and potential toxic outcomes is crucial for
evaluating the overall impact of dehalogenation reactions in xenobiotic biotransformation.

5.2.6 Epoxidation Reactions

Epoxidation reactions within xenobiotic biotransformation involve the formation of
epoxides—three-membered cyclic ethers. Cytochrome P450 enzymes, renowned for their
versatility, are instrumental in catalyzing epoxidation reactions. This process is particularly
significant in the metabolism and detoxification of xenobiotics, including environmental
pollutants and certain drugs.

Role of Cytochrome P450 Enzymes in Epoxidation

Cytochrome P450 enzymes, embedded in the endoplasmic reticulum of cells, serve as
catalysts for epoxidation reactions. These enzymes activate molecular oxygen, leading to
the formation of reactive oxygen species, which then participate in the formation of
epoxides from substrates.

Examples of Epoxidation Reactions

1. Epoxidation of Benzo[a]pyrene
• Catalyst: Cytochrome P450 Enzymes
• Outcome: Formation of epoxides from benzo[a]pyrene, a polycyclic aromatic
hydrocarbon.
• Significance: This epoxidation reaction is crucial for the metabolism and
detoxification of environmental pollutants.

Mechanism of Epoxidation Reactions

1. Substrate Binding
The xenobiotic substrate binds to the active site of a cytochrome P450 enzyme.

2. Oxygen Activation

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Molecular oxygen (O2) is activated within the enzyme's active site, leading to the formation
of a reactive oxygen species.

3. Epoxidation
The activated oxygen species reacts with the substrate, introducing an oxygen atom
between two adjacent carbon atoms, resulting in the formation of a cyclic epoxide.

4. Product Formation
The epoxidated product, now modified and often more water-soluble, is released from the
enzyme.

Significance in Detoxification
Epoxidation reactions are crucial for the detoxification of xenobiotics, as the resulting
epoxides are often more polar and water-soluble than their parent compounds. This
modification facilitates the excretion of the substrate from the body.

Integration with Phase I Reactions

Epoxidation is an integral part of Phase I reactions, contributing to the overall diversity of
transformations that xenobiotics undergo during their initial metabolic processing. It often
occurs alongside other oxidative reactions mediated by cytochrome P450 enzymes.

Challenges and Considerations

While epoxidation reactions are generally associated with detoxification, some epoxides
can be highly reactive and potentially toxic. Therefore, understanding the balance between
beneficial detoxification and potential adverse effects is crucial for evaluating the overall
impact of epoxidation reactions in xenobiotic biotransformation.

5.2.7 N-Oxidation Reactions

N-Oxidation reactions within xenobiotic biotransformation involve the introduction of
oxygen to nitrogen atoms in substrates. Cytochrome P450 enzymes, known for their diverse
catalytic activities, play a significant role in catalyzing N-oxidation reactions. This process is
crucial for the metabolism and detoxification of xenobiotics, including drugs and
environmental compounds.

Role of Cytochrome P450 Enzymes in N-Oxidation

Cytochrome P450 enzymes, located in the endoplasmic reticulum of cells, serve as catalysts
for N-oxidation reactions. These enzymes activate molecular oxygen, leading to the
formation of reactive oxygen species, which then participate in the oxidation of nitrogen
atoms in substrates.

Examples of N-Oxidation Reactions

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1. N-Oxidation of Aromatic Amines:

• Catalyst: Cytochrome P450 Enzymes

• Outcome: Introduction of oxygen to nitrogen atoms in aromatic amines.
• Example: N-Oxidation of diphenylamine, a process contributing to the metabolism
of certain drugs.

Mechanism of N-Oxidation Reactions

1. Substrate Binding
The xenobiotic substrate, typically containing an aromatic amine group, binds to the active
site of a cytochrome P450 enzyme.

2. Oxygen Activation
Molecular oxygen (O2) is activated within the enzyme's active site, leading to the formation
of a reactive oxygen species.

3. N-Oxidation
The activated oxygen species reacts with the nitrogen atom in the substrate, introducing an
oxygen atom and resulting in the formation of an N-oxide.

4. Product Formation
The N-oxidized product, now modified and often more water-soluble, is released from the
enzyme.

Significance in Detoxification
N-Oxidation reactions contribute to the detoxification of xenobiotics by enhancing their
water solubility. The resulting N-oxides are often more polar and easily excreted from the
body.

Integration with Phase I Reactions

N-Oxidation is an integral part of Phase I reactions, contributing to the overall diversity of
transformations that xenobiotics undergo during their initial metabolic processing. It often
occurs alongside other oxidative reactions mediated by cytochrome P450 enzymes.

Challenges and Considerations

While N-oxidation reactions are generally associated with detoxification, some N-oxides
can be reactive and potentially toxic. Therefore, understanding the balance between
beneficial detoxification and potential adverse effects is crucial for evaluating the overall
impact of N-oxidation reactions in xenobiotic biotransformation.

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5.2.8 S-Oxidation Reactions

S-Oxidation reactions within xenobiotic biotransformation involve the introduction of
oxygen to sulfur atoms in substrates. Cytochrome P450 enzymes, known for their versatile
catalytic activities, play a significant role in catalyzing S-Oxidation reactions. This process is
crucial for the metabolism and detoxification of xenobiotics containing sulfur groups.

Role of Cytochrome P450 Enzymes in S-Oxidation

Cytochrome P450 enzymes, located in the endoplasmic reticulum of cells, serve as catalysts
for S-Oxidation reactions. These enzymes activate molecular oxygen, leading to the
formation of reactive oxygen species, which then participate in the oxidation of sulfur atoms
in substrates.

Examples of S-Oxidation Reactions

1. S-Oxidation of Thioether-Containing Drugs

• Catalyst: Cytochrome P450 Enzymes
• Outcome: Introduction of oxygen to sulfur atoms in thioether-containing drugs.
• Example: S-Oxidation of certain drugs containing thioether groups.

Mechanism of S-Oxidation Reactions

1. Substrate Binding
The xenobiotic substrate, typically containing a sulfur atom in a thioether group, binds to
the active site of a cytochrome P450 enzyme.

2. Oxygen Activation
Molecular oxygen (O2) is activated within the enzyme's active site, leading to the formation
of a reactive oxygen species.

3. S-Oxidation
The activated oxygen species reacts with the sulfur atom in the substrate, introducing an
oxygen atom and resulting in the formation of an S-oxide.

4. Product Formation
The S-oxidized product, now modified and often more water-soluble, is released from the
enzyme.

Significance in Detoxification
S-Oxidation reactions contribute to the detoxification of xenobiotics by enhancing their
water solubility. The resulting S-oxides are often more polar and easily excreted from the
body.

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Integration with Phase I Reactions

S-Oxidation is an integral part of Phase I reactions, contributing to the overall diversity of
transformations that xenobiotics undergo during their initial metabolic processing. It often
occurs alongside other oxidative reactions mediated by cytochrome P450 enzymes.

Challenges and Considerations

While S-Oxidation reactions are generally associated with detoxification, some S-oxides can
be reactive and potentially toxic. Therefore, understanding the balance between beneficial
detoxification and potential adverse effects is crucial for evaluating the overall impact of S-
Oxidation reactions in xenobiotic biotransformation..

5.3 Examples of Phase I Reactions in Drug Metabolism

1. Paracetamol (Acetaminophen)
Phase I Reaction: Hydroxylation by CYP450 enzymes.

Outcome: Formation of a reactive metabolite, which, in excessive amounts, can lead to

hepatotoxicity.

2. Caffeine
Phase I Reaction: N-Demethylation by CYP450 enzymes.

Outcome: Formation of dimethylxanthine (theobromine), contributing to the stimulating

effects of caffeine.

3. Benzodiazepines (e.g., Diazepam)

Phase I Reaction: Oxidative metabolism via CYP450 enzymes.

Outcome: Formation of hydroxylated metabolites with altered pharmacological activity.

4. Codeine
Phase I Reaction: O-Demethylation by CYP450 enzymes.

Outcome: Formation of morphine, which contributes to codeine's analgesic effects.

5.4 Importance of Phase I Reactions

1. Activation of Prodrugs
Some drugs are administered in an inactive form and undergo phase I reactions to become
pharmacologically active.

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2. Toxicity Reduction
Phase I reactions can generate less toxic metabolites, aiding in the detoxification process.

3. Formation of Reactive Intermediates

While some reactive metabolites can be toxic, others are crucial for the elimination of
xenobiotics.

4. Substrate Specificity
Different enzymes within the cytochrome P450 family exhibit specificity for certain
substrates, contributing to the diversity of phase I reactions.

In summary, phase I reactions in xenobiotic biotransformation involve a variety of enzymatic

processes that introduce or expose functional groups, making the xenobiotics more
amenable to subsequent phase II reactions. These reactions are pivotal in drug metabolism,
environmental detoxification, and the body's defense against potentially harmful
substances. Understanding these processes is essential in pharmacology, toxicology, and
the development of therapeutic interventions.

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