Amino acid conjugation

Amino acid conjugation is a significant metabolic route for a number of carboxylic acids and involves the formation of an amide bond between the xenobiotic acyl-CoA and the amino acid. Glycine is the amino acid most frequently used for conjugation of small aromatic acids (reaction A in Figure 19), while a few glutamine conjugates (reaction B in Figure 19) have been characterized in humans. In addition, taurine (reaction C in Figure 19) and perhaps a few other amino acids and dipeptides can be used for conjugation in various animal species.37 The enzymes catalyzing these transfer reactions are known or believed to be various N-acyltransferases, for example:

• glutamine N-phenylacetyltransferase (EC 2.3.1.14);

• glycine N-benzoyltransferase (EC 2.3.1.71); and

• bile acid-CoA:amino acid N-acyltransferase (EC 2.3.1.65; glycine-taurine N-acyltransferase).

The xenobiotic acids undergoing glycine conjugation are mainly substituted benzoic acids, e.g., benzoic acid itself (55, Figure 20); the discovery of hippuric acid, its glycine conjugate, in the urine of horses over 150 years ago marks the birth of the science of drug metabolism. Salicylic acid (56) similarly yields salicyluric acid, which accounts for about 3/4 of a dose of aspirin in humans. Similarly, m-trifluoromethylbenzoic acid (57), a major metabolite of fenfluramine, is excreted as the glycine conjugate. A number of studies have been published on the structure-metabolism relationships of benzoic acid derivatives and analogs in glycine conjugation.98,101

Benzoic Acid Conjugation With Glycine

Figure 19 Metabolic conjugations involving acyl-CoA intermediates of xenobiotic acids, namely conjugation to glycine (reaction A), glutamine (reaction B), taurine (reaction C), and cholesterol (reaction D), and formation of hybrid triglycerides (reaction E).

Figure 19 Metabolic conjugations involving acyl-CoA intermediates of xenobiotic acids, namely conjugation to glycine (reaction A), glutamine (reaction B), taurine (reaction C), and cholesterol (reaction D), and formation of hybrid triglycerides (reaction E).

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Responses

  • sara
    What is conjugation of metabolites?
    8 years ago
  • torin
    Which drug is metabolized by aminoacid conjugation?
    10 months ago
  • tori
    Why are few drugs metabolised by amino acid conjugation?
    2 months ago

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