Reduction
This is the second type of phase II reaction. The gain of an electron by the substrate
in a chemical reaction is termed as reduction reaction. The reducing agent refers to
the element that accepts electrons and in the reaction, one compound is oxidized and
another compound is reduced. The reactions are most likely to occur in xenobiotics
with low oxygen content. Reductions can take place across nitrogen–nitrogen double
bonds, termed as azo reduction, or on nitro groups (NO 2 ). Commonly, the resultant
amino compounds get oxidized to form toxic metabolites. In biological tissues,
carbon tetrachloride can be reduced to free radicals which are very harmful to the
body. So, the reduction reactions frequently result in inactivation of a xenobiotic
rather than detoxification (Lech and Vodicnik 1985; David et al. 2005). An example
of a reduction reaction in which the nitro group is reduced is illustrated in Fig. 16.1.
Most of the reduction reactions are explained by the name of the reaction or
enzyme involved. Few of these reduction reactions are as follows:
• Azo reduction
• Dehalogenation
• Disulfide reduction
• Nitro reduction
• N-oxide reduction
• Sulfoxide reduction
Examples of drugs which undergo reduction include a prodrug called prednisone,
which is reduced to the active glucocorticoid prednisolone; warfarin, an
anticoagulant.
Hydrolysis
It is the final reaction of phase I. The hydrolysis reaction is breaking of toxicant into
two fragments or smaller molecules when a water molecule is used to break the
bond. The hydroxyl group (OH–) is attached into one fragment and the hydrogen
atom is attached into the other fragment (Lech and Vodicnik 1985; David et al.
2005). These hydrolysis reactions mainly happen between an ion and water.
Example In a biotransformation reaction, the procaine compound produces two
major smaller chemicals (Fig. 16.2).
Fig. 16.1 Reduction reaction
in which the nitro group is
reduced (from NO 2 to NH 2 )
16 Biotransformation: Basics and Applied Perspectives
341
This is the second type of phase II reaction. The gain of an electron by the substrate
in a chemical reaction is termed as reduction reaction. The reducing agent refers to
the element that accepts electrons and in the reaction, one compound is oxidized and
another compound is reduced. The reactions are most likely to occur in xenobiotics
with low oxygen content. Reductions can take place across nitrogen–nitrogen double
bonds, termed as azo reduction, or on nitro groups (NO 2 ). Commonly, the resultant
amino compounds get oxidized to form toxic metabolites. In biological tissues,
carbon tetrachloride can be reduced to free radicals which are very harmful to the
body. So, the reduction reactions frequently result in inactivation of a xenobiotic
rather than detoxification (Lech and Vodicnik 1985; David et al. 2005). An example
of a reduction reaction in which the nitro group is reduced is illustrated in Fig. 16.1.
Most of the reduction reactions are explained by the name of the reaction or
enzyme involved. Few of these reduction reactions are as follows:
• Azo reduction
• Dehalogenation
• Disulfide reduction
• Nitro reduction
• N-oxide reduction
• Sulfoxide reduction
Examples of drugs which undergo reduction include a prodrug called prednisone,
which is reduced to the active glucocorticoid prednisolone; warfarin, an
anticoagulant.
Hydrolysis
It is the final reaction of phase I. The hydrolysis reaction is breaking of toxicant into
two fragments or smaller molecules when a water molecule is used to break the
bond. The hydroxyl group (OH–) is attached into one fragment and the hydrogen
atom is attached into the other fragment (Lech and Vodicnik 1985; David et al.
2005). These hydrolysis reactions mainly happen between an ion and water.
Example In a biotransformation reaction, the procaine compound produces two
major smaller chemicals (Fig. 16.2).
Fig. 16.1 Reduction reaction
in which the nitro group is
reduced (from NO 2 to NH 2 )
16 Biotransformation: Basics and Applied Perspectives
341