After William’s theory, many researchers proved his concept and end up developing the thought that phase I reactions must by necessity precede phase II.
However, in some of the cases, the metabolic process can bypass all phase I chemical
manipulations and undergo conjugation, i.e. phase II reaction directly (David et al.
2005).
16.3.2.1 Phase I Reactions
In general, phase I reactions are reactions which modify the chemical by adding a
functional structure which is usually a small polar group which contains both
positive (+ve) and negative (Àve) charges (Lech and Vodicnik 1985). The addition
of a functional group permits the substance to fit into the enzymes of phase II
reaction. The phase I reactions are further classified into:
1. Oxidation
2. Reduction
3. Hydrolysis
Oxidation
It is the most common reaction of phase I. It is correctly defined as a process where
the substrate loses electrons. There are a number of reactions which have the ability
to remove electrons from the substrate but because the addition of oxygen, or
oxygenation, was the first discovered so it was named oxidation. However, most
of the oxidation reactions do not involve oxygen (Lech and Vodicnik 1985; David et
al. 2005).
Example Dehydrogenation is one of the examples of the oxidation reaction, which
removes the hydrogen from the molecule. Most of the oxidizing reactions are
explained by the name of the reaction or enzyme involved. Few of these oxidation
reactions are as follows:
• Alcohol dehydrogenation
• Alkyl/acyclic hydroxylation
• Aromatic hydroxylation
• Deamination
• Desulfuration
• N-dealkylation
• N-hydroxylation
• N-oxidation
• O-dealkylation
• Sulfoxidation
The drugs which undergo oxidative metabolism include ropivacaine, paracetamol, omeprazole codeine, and phenothiazines.
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M. H. Yashavarddhan et al.
However, in some of the cases, the metabolic process can bypass all phase I chemical
manipulations and undergo conjugation, i.e. phase II reaction directly (David et al.
2005).
16.3.2.1 Phase I Reactions
In general, phase I reactions are reactions which modify the chemical by adding a
functional structure which is usually a small polar group which contains both
positive (+ve) and negative (Àve) charges (Lech and Vodicnik 1985). The addition
of a functional group permits the substance to fit into the enzymes of phase II
reaction. The phase I reactions are further classified into:
1. Oxidation
2. Reduction
3. Hydrolysis
Oxidation
It is the most common reaction of phase I. It is correctly defined as a process where
the substrate loses electrons. There are a number of reactions which have the ability
to remove electrons from the substrate but because the addition of oxygen, or
oxygenation, was the first discovered so it was named oxidation. However, most
of the oxidation reactions do not involve oxygen (Lech and Vodicnik 1985; David et
al. 2005).
Example Dehydrogenation is one of the examples of the oxidation reaction, which
removes the hydrogen from the molecule. Most of the oxidizing reactions are
explained by the name of the reaction or enzyme involved. Few of these oxidation
reactions are as follows:
• Alcohol dehydrogenation
• Alkyl/acyclic hydroxylation
• Aromatic hydroxylation
• Deamination
• Desulfuration
• N-dealkylation
• N-hydroxylation
• N-oxidation
• O-dealkylation
• Sulfoxidation
The drugs which undergo oxidative metabolism include ropivacaine, paracetamol, omeprazole codeine, and phenothiazines.
340
M. H. Yashavarddhan et al.