Metabolism of Xenobiotics :
Metabolism of Xenobiotics Xenobiotics - Foreign chemicals
(Drugs, Food additives, Pollutants etc)
These Xenobiotics must be metabolized and should be excreted, if they stay longer time they damage the cells.
Metabolism of Xenobiotics in two phases :
Metabolism of Xenobiotics in two phases Phase 1 Includes Hydroxylation
Reduction
Dehalogenation
Desulfation
Deamination
Hydrolysis
Phase 2 Hydroxylated or other compounds produced in Phase I are converted to polar metabolites by conjugation c glauconitic acid, sulfate, acetate, glutathione.
In phase I the Major reaction is Hydroxylation, catalyzed by Mono Oxygenases or Cytochrome P450 s or Mixed function oxidases. :
In phase I the Major reaction is Hydroxylation, catalyzed by Mono Oxygenases or Cytochrome P450 s or Mixed function oxidases. These are various Insoforms of cytochrome P450 s The basic reaction is
RH + O2 + NADPH + H + R – OH + H2o + NADP
RH represents - Drugs
Carcinogens
Pesticides
Petroleum products, Pollutants.
Endogenous compounds certain steroids
Eicosonoids
retenoids
Generally the substrates are Lipophillic after Hydroxylation they are Hydrophillic
Slide 5:
Cytochome P450`
Mainly located in Liver and also present in most of the cells.
Seen over Endoplasmic retrculum or in Mitochendisa.
These are considered as Versalite catalysts
Hemoproteins
Many Isoforms are Inducible
Their levels are decreased in chronic liver disorders ( Cirrhosis)
Its role is dependent on NADPH
Examples for Phase I :
Examples for Phase I Methanol Formic acid
Ethanol Acetic acid
Benzal dehyde Benzoic acid
Chloral Trichloloacetic acid
Aniline P – Amino phenol
Picric acid Picramic acid
Asprin Salicylicacid + Acetic acid
Procaine P- aminobezoic acid +
Diethylamino ethanol
Conjugation :
Conjugation The products of phase I reaction are conjugated with Glucoronic acid, sulfate or Glutatheoric
This makes the compound even more water soluble and they are excreted in urine or bile.