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Phase 1 metabolism
The major phase 1 reactions are oxidation, reduction, and
hydrolysis, exposing or introducing a functional group (-OH)
to increase reactivity and slightly increase hydrophilicity.
Cytochrome P450:
Cytochrome P450 (CYP) enzymes are the most important in
biotransformation in terms of the catalytic versatility and
number of xenobiotics that it metabolizes: 400 isozymes and
36 families.
Oxidation
The majority of these reactions are catalyzed by one enzyme
system, the cytochrome P450 mono-oxygenase.
The liver has the highest concentration of this enzyme although
it can be found in most, if not all tissues.
The reactions catalyzed also require NADPH, molecular oxygen
and magnesium,
Reduction
Reductases in the microflora present in the gastrointestinal
tract has an important role in the reduction of xenobiotics.
There are a number of different reductases, which can catalyze
the reduction of azo and nitro compounds.
Reduction of the azo dye prontosil to produce the antibacterial
drug sulfanilamide is a well-known example of azo reduction.
Phase 2 Metabolism
Sulfation
The addition of the sulphate moiety to a hydroxyl group is a
major route of conjugation for foreign compounds.
It is catalyzed by a cytosolic sulphotransferase enzyme and
utilizes the coenzyme phosphoadenosine phosphosulphate.
The product is an ester which is very polar and water soluble.
Glucuronidation
Glucuronic acid is a polar and water soluble carbohydrate
molecule which may be added to hydroxyl groups, carboxylic
acid groups, amino groups and thiols.
This process is a major route of phase 2 metabolism and utilizes
glucuronosyl transferases, which are microsomal enzymes, with
uridine diphosphate glucuronic acid as the cofactor.
References
Timbrell, J. A. 2009. Principles of Biochemical Toxicology.
Informa Healthcare(USA).
Timbrell, J. 2002. Introduction to Toxicology. Taylor &
Francis Inc, London.
www.xenotechllc.com/chapter-6
nature.berkeley.edu/~dnomura/pdf/Lecture4MetabolismPhaseI
v2.pdf
nature.berkeley.edu/~dnomura/pdf/Lecture5Meta
bolismPhaseII.pdf