Conjugation

First, let us learn what is metabolism of xenobiotics..

  • Detoxification –

    The series of biochemical reactions occurring in the body to convert foreign compounds to non-toxic and more easily excretable form.

  • Xenobiotic is any foreign or strange substance to the body.
  • Detoxification of this is called metabolism of xenobiotics.
  • The metabolism of xenobiotics is divided into 2 phases –
  1. Reactions are – oxidation, reduction, hydrolysis.
  2. Conjugation reactions.

 

Let us study conjugation in details.

Conjugation is a process in which a foreign substance combines with a substance produced in the  body.

The combined product is then easily detoxified & excreted from the body.

 

  • Few examples of important conjugating agents –

 

1.Glucuronic acid :

  • This is the most common.
  • The active form of glucoronic acid is UDP-glucoronic acid in uronic acid pathway.
  • UDP-glucuronyltransferasesare the enzymes which participate in glucuronide formation.
  • It occurs with compounds containing hydroxyl , carbonyl, sulfhydryl or amino groups.
  • Strongly acidic compounds which are more soluble in water are produced – hence more easily excreted.

2.Glycine

  • Aromatic carboxylic acids are conjugated with glycine.
  • When benzoyl CoA is conjugated with glycine, hippuric acid is formed.

3.Glutamine :

  • Is relatively less important.
  • Phenylacetic acid is conjugated with glutamine to form phenylacetyl glutamine.

4.Methylgroup :

  • Methyl group of S-adenosylmethionine is used to methylate many compounds.

Enzyme methyl transferase is used.

5.Sulfate:

  • The active form 3’-phosphoadenosine 5- phosphosulfate(PAPS)participates in conjugation.
  • Enzyme sulfotransferase in involved.
  • Aliphatic & aromatic compounds undergo sulfation.

 

6.Acetic acid :

-Acetyl CoA is the active form .

– Drugs like sulfanilamide are converted to acetyl derivatives.

 

7.Thiosulfate :

  • Highly toxic cyanides are conjugated with thiosulfate to form less toxic thiocyanate.

8.Glutathione :

  • Glutathione is a tripeptide.
  • A wide range of organic compounds such as alkyl or aryl halides, alkenes and epoxides are conjugated with cysteine of glutathione.
  • The conversion of bilirubin to conjugated bilirubin is an example of conjugation with glucuronide.
    • Bilirubin combines with UDP – glucuronic acid to form bilirubin-diglucuronide.

 

Contributed by

Soumya Khot- GMC, Kolhapur.

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