Xenobiotics

xenobiotics


  • A xenobiotic is a compound that is foreign to the body
  • may be accidentally ingested or taken as drugs or compounds produced in the body by bacterial metabolism (Greek, xenos = strange).
  • They are  metabolized,  a process called  biotransformation(detoxification).
  • Metabolism  of  xenobiotics  in  two  phases (phase I and phase II).
  • The cytochrome P450 enzymes are involved in the biotransformation reactions, the most important  enzyme present on smooth endoplasmic reticullum.
  • They are heme containing enzymes, localized in the endoplasmic reticulum of liver.
  • so, Liver  is  the  major site  for  metabolism  of xenobiotics.
  • Cytochrome P450 contains phosphatidyl choline.
  • Phase one is the alteration of the foreign molecule, so as to add a functional group.
  • The products of metabolic transformations are either excreted directly or undergo further meta-bolism by phase two reactions.

Phase |  (non-synthetic)  reactions

1. Oxidative Reactions:

  • metabolism of compounds by oxidation (including hydroxylation), reduction, hydrolysis, cyclization and decyclization.
  • The oxidation and detoxification of alcohol is also an important function of the liver.
  • the alcohol dehydrogenase is an NAD linked enzyme, which is located in the cytosol. Aldehyde dehydrogenase is an NAD+dependent mitochondrial enzyme.

2. Reduction Reactions: 

  • compounds which are reduced and detoxified by the liver are nitro compounds, These are reduced to their amines, while aldehydes or ketones are reduced to alcohols.

3. Hydrolysis:

  • addition of water splits the toxicant into two fragments or smaller molecules., 
  • Esters, amines,hydrazines, amides, glycosidic bonds and carba-mates are generally biotransformed by hydrolysis.

PHASE TWO REACTIONS; CONJUGATIONS:

  • a new metabolite from phase 1  contains a reactive chemical group, e.g. hydroxyl (-OH),amino (-NH2), and carboxyl (-COOH).
  • Glucuronide conjugation is the most common Phase two reactions. Bilirubin is a good example for a compound conjugated and excreted as its glucuronide.
  • Formation of bilirubin diglucuronide is a normal metabolic reaction for detoxification of bilirubin by phase 2 reactions.
  • The glucuronic acid is added to xenobiotics by UDP-glucuronyl transferases, present in the endo-plasmic reticulum.
  • sulfation decreases the toxicity of xenobiotics, for eg Phenolic and alcoholic compounds are conju-gated with sulfate.(steroids and indole compounds.)
  • cysteine is derived from glutathione, which is the active conjugating agent,
  • For example, catechol-O-methyl transferase converts epinephrine to metanephrine. Pyridine is excreted as N-methyl pyridine.
  • Mercapto ethanol is excreted as 5-methyl mercapto ethanol.

Exam Important

  • metabolism of compounds by oxidation (including hydroxylation), reduction, hydrolysis, cyclization and decyclization.
  • The oxidation and detoxification of alcohol is also an important function of the liver.
  • Bilirubin is a good example for a compound conjugated and excreted as its glucuronide.
  • Formation of bilirubin diglucuronide is a normal metabolic reaction for detoxification of bilirubin by phase 2 reactions.
  • The glucuronic acid is added to xenobiotics by UDP-glucuronyl transferases, present in the endo-plasmic reticulum.
  • catechol-O-methyl transferase converts epinephrine to metanephrine. Pyridine is excreted as N-methyl pyridine.
Don’t Forget to Solve all the previous Year Question asked on xenobiotics

Module Below Start Quiz

Leave a Reply

Free Mini Course on Stomach

Mini Course – Stomach

22 High Yield Topics in Stomach

in Just 2 Hours

Submission received, thank you!

Close Window
%d bloggers like this:
Malcare WordPress Security