- Conjugation means chemical combination of one substance with the other.
- Xenobiotics undergo conjugation to produce less toxic and/or more polar (water soluble) and thus easily excretable(through bile, urine) compounds.
- It may occur without prior metabolism of Phase-I reactions but is more common as a Phase-II reaction.
- Many conjugating agents are known like glucuronic acid, glutamine, glutathione, etc.
Conjugation with Glucuronic Acid
- Most common form of conjugation.
- Glucuronic Acid participates in its active form- UDP Glucuronic Acid
- Microsomal enzyme UDP-Glucoronyl transferase catalyzes the reaction.
- Xenobiotics –> XO Glucuronide
- Bilirubin–> Bilirubin diglucuronide
Conjugation with Glycine
- Many Aromatic Acids conjugate with glycine.
- Glycine + Benzoic Acid = Hippuric Acid
- Similarly, Glycine +
- Salicylic Acid = Salicyliuric Acid
- Nicotinic Acid = Nicotinuric Acid
- Cholic Acid = Glycocholic Acid
- Deoxycholic Acid = Deoxyglycocholic Acid
Conjugation with Glutamine
- Phenylacetic Acid + Glutamine = Phenylacetylglutamine
Conjugation with Glutathione(GSH)
- GSH = Gamma-glutamyl-cysteinyl-glycine
- Glutathione is a tripeptide of Glutamic Acid, Cysteine and Glycine
- Xenobiotics conjugate with glutathione to form glutathione conjugates which are further metabolized and excreted in the form of Mercapturic Acid.
- Xenobiotics conjugating with glutathione are-
- Aromatic nitro compounds
- Halogenated compounds
- Aliphatic halides
- Phase I epoxides
Conjugation with Sulphate(Sulphation)
- Active form of sulphate-PAPS-Phosphoadenosyl Phosphosulphate is the sulfur donor in the reaction.
- Enzyme involved is Sulfotransferase
- PAPS + Xenobiotic = Sulfated Xenobiotic(Ethereal Sulphate) + PAP
- Several aliphatic and aromatic compounds(E.g. Phenol) undergo detoxification
Conjugation with Thiosulphate
- Tiny amounts of highly toxic Cyanides formed during normal metabolism are conjugated with thiosulphate to form relatively non-toxic thiocyanate.
- Enzyme involved is Rhodanese(Thiosulphate-sulphur-transferase)
- HCN + Sodium Thiosulphate = Thiocyanate + Sodium Sulphate
Conjugation with Acetic Acid (Acetylation)
- Active form of Acetic Acid, i.e., Acetyl CoA takes part.
- Catalyzing enzyme is Acetyltransferase
- Acetyl CoA + X = Acetyl-X + CoA
- Compounds that undergo acetylation-
- Sulpha Drugs like Sulphanilamide
- Anti-TB drugs like Isoniazid
- PABA: Para aminobenzoic Acid
Conjugation by Methylation
- Active form of Methionine, i.e., S-Adenosyl Methionine takes part.
- Enzyme involved is Methyltransferase
- Compounds undergoing methylation:-
- Pyridine
- Nicotinic Acid
- Nicotinamide
- Thyroxine
- Estrogen
- Epinephrine
- Norepinephrine
Conjugation with Cysteine
- Cysteine + Acetic Acid = Acetyl Cysteine
- Xenobiotics + Acetyl Cysteine = Nontoxic Mercapturic Acids
- Compounds undergoing conjugation with cysteine are:-
- Bromobenzene
- Chlorobenzene
- Iodobenzene
- Naphthalene
- Anthracene
- Anthracene
- Benzyl Chloride
Conjugation with BAL
- British Antilewisite
- 2,3-Mercaptopropanol
- Antidote for heavy metals like Arsenic, Cadmium, Gold and Mercury which were present in Lewisite which was used in World War I.