Amino acid conjugates formation

Although this pathway involves the formation of an AMP adduct similar to the amino acid conjugation pathway, it is really not a conjugation pathway because the result is simply the inversion of configuration. 

Figure 10.6 The intramolecular interstrand H-bonding pattern in amino acid conjugates of disubstituted Fc derivatives results in the formation of 10-membered rings for ferrocene dicarboxylic acid conjugates, 12-membered rings forFca-conjugates, and 14-membered rings for ferrocenediamine conjugates. Reproduced by permission from Ref. 50 of The Royal Society of Chemistry.

Generally amino acid conjugation is a detoxication reaction. However, amino acid conjugation with hydroxylamino groups (N-hydroxy) can lead to the formation of reactive nitrenium ions, as already discussed with sulfate conjugation and acetylation. For example, the conjugation of serine with N-hydroxy-4-aminoquinoline-l-oxide (Fig. 4.40 for structure) leads to such a reactive nitrenium ion. This requires the enzyme serine-tRNA synthetase. 

The largest group of amino acid conjugates studied, except for cysteine conjugates, consists of a diversity of carboxylic acids bound to different amino acids via an amide bond. The enzymatic formation of this type of amino acid conjugates, examples of carboxylic acid compounds and amino acids determined to undergo... 

The formation of an amide bond by organic chemical methods Is usually accomplished by reacting the acid halogenlde and the amino acid unless the acid substrate contains other reactive groups. The acid chloride Is prepared directly with thlonyl chloride (244) or Indirectly via the formation of a mixed anhydride by use of another acid halogenlde (245,246). Isotoplcally labeled [(2,4-Dlchlorophenoxy)acetyl]valine was synthesized by a DCC catalyzed reaction between the acid and valine (247). A few examples of synthetic amino acid conjugates of xenobiotics are shown In Table X. Several taurine conjugates of both alkanolc and benzylic acids have been synthesized and their physical properties determined by Idle et al. (2 ). 

A mechanism for hepatic formation of amino acid conjugates of bile acids developed from early investigations of Siperstein and Murray [37], Bremer [38], and Elliott [39] is summarized as follows ... 

The metabolism of xenobiotic carboxylic acids to amino acid conjugates involves a two-step enzymatic pathway in which the xenobiotic is first activated in an ATP-dependent reaction to the corresponding coenzyme A thioester. This in turn serves as the substrate for an N-acyltransferase that catalyzes the formation of the peptide bond... 

Formation of these amino acid conjugates is catalysed by p-(9-cytokinin)-aIanine synthase, classified as C-N ligase, and characterised in lupin seeds [134]. The enzyme requires O-acetylserine as donor of the alanine moiety and recognises all main cytokinin bases (including BA) and many other purine derivatives as substrates. Similarly to cytokinin 7- and 9-glucosides, also cytokinin 9-alanyl derivatives are biologically inactive and metabolically stable, and are therefore candidates to be cytokinin-inactivation and detoxification products. 

Studies of 2.4.5-T [(2,4,5-trichlorophenoxy)acetic acid] metabolism in soybean callus tissue also showed that formation of amino acid conjugates was a major metabolic fate of the herbicide... 

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