Phases of biotransformation/detoxification:
Detoxification or biotransformation reactions are generally classified into two phases :
- Phase one : in this phase the compounds are made less toxic with the help of oxidation, hydroxylation etc. reactions.
- Phase two: in this phase the less toxic compounds formed by phase one are conjugated with othe compounds and they are excreted out.
Phase one reactions:
- Oxidation : it involves hydroxylation reaction carried out by the enzyme mixed oxidase system.
Example : toluene is hydroxylated to benzyl alcohol.
- Reduction: it involves the reduction of nitro compounds. The nitro compounds are reduced to their amines where as aldihydes are reduced to the alcohols.
Example: reduction of nitrobenzene to aniline.
- Hydrolysis: it is the reaction where there is addition of water molecule and this splits the toxic compound into smaller fragmants.
Example: hydrolysis of acetyle choline into choline and acetyl coA
Phase two reactions:
- Conjugation : phase two reactions are conjugation reactions i.e. new compound is added to the metabolite produced by the phase one reaction. The conjugation reactions can be:
- Glucuronic acid conjugation: glucuronic acid is conjugated with bilirubin to make the bilirubin water soluble so that it can be easily excreted.
- Sulfate conjugation: addition of sulfur can reduce the toxicity of some compounds. Some phenol containing compounds can be conjugated with sulfur to make less toxic.
- Acetylation: conjugation of some drugs like isoniazide with acetic acid is called as acetylation.
- Conjugation with glycine: benzoic acid is conjugated with glycine to form hippuric acid and this is excreted through the urine.