Amino acids conjugation with

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 chemistry of conjugates of amino acids with metal complexes has been summarized by Beck and coworkers [20], Also, it is beyond the scope of this review to include all amino acid conjugates with metal complexes. We will only touch a few... 

Plants. In tolerant plants, readily metabolized to hydroxyatrazine and amino acid conjugates, with further decomposition of hydroxyatrazine by degradation of side-chains and hydrolysis of resulting amino acids on the ring together with evolution of C02... 

In 1995 Nicolaou and coworkers initiated a renaissance in the construction of sugar amino acid conjugates with their synthesis of carbonucleotoids [49]. Although they did not prepare amide-linked carbohydrates, they did introduce the term carbopep-toid to designate such materials. Shortly thereafter, a number of papers directed toward the synthesis of carbopeptoids appeared. One of the earliest was reported by Wessel et al., who used nor-muramic acid derivatives and condensed them in solution by means of 2-chloro-4,6-dimethoxy-l,3,5-triazine (CDMT) in DMF to construct a tetramer (Fig. 27). 

The phenolates are based on the iron binding capacity of 2,3-DHBA or SA. These siderophores range in structure from the free monomer 2,3-DHBA or SA which form Fe(2,3-DHBA)3 or Fe(SA)3 complexes [61-64], to single amino acid conjugates with for instance serine, glycine, cysteine, and lysine [55,65-70], and even more complex molecules like enterobactin (cyclic triester of 2,3-DHBA-serine) [71-73]. 

Conjugation with amino acids is a major route of metabolism for carboxylic acids including aromatic, heteroaromatic, arylacetic, cinnamic, and arylox-yacetic acids. Although a wide range of amino acid conjugates has been ob-... 

In most conjugations, it is the cofactor that is activated, but in amino acid conjugation it is the substrate that is activated, first by reacting with ATP to form an AMP conjugate, which is further converted to a CoA thio ester as shown in Figure 7.13. 

Many nonsteroidal anti-inflammatory drugs (NSAIDs) are substituted 2-arylpropionic acids. Most NSAIDs also have a chiral carbon next to the carboxylate and are administered as a racemic mixture of the two enantiomers. In general, the (S)-enantiomcr is responsible for most of the antiinflammatory activity of these agents. It was found that the (/ -enantiomer is converted to the (S)-enantiomer but the reverse does not occur (23). As with amino acid conjugation, the pathway involves reaction with ATP to form an AMP ester, which is, in turn, converted to a Co-A ester, and it is the Co-A ester that undergoes chiral inversion (Fig. 7.14). Substrates include ibuprofen, naproxen, and fenoprofen. 

Polymastiamide A (579), an antimicrobial steroid with an unusual side chain modification involving an amide bond to a non-protein amino acid, was isolated from the Norwegian marine sponge Polymastia boletiformis. The structure of polymastiamide A (579) was elucidated by analysis of spectroscopic data and chemical interconversions [470]. Polymastiamides B-F (580-584), additional amino acid conjugates of steroids, were later isolated from the same sponge [471],... 

Although bile acid conjugates with amino acids are normally excreted into bile, amino acid conjugates of xenobiotics are usually excreted into urine. Conjugation with endogenous amino acids facilitates urinary excretion because of the organic anion transport systems located in the kidney tubules. 

Conjugation involves addition of an endogenous moiety to a foreign molecule, which may be a product of a phase 1 reaction. Major phase 2 routes conjugation with glucuronic acid, sulfate, glutathione amino acids acetylation methylation. Enzymes involved are transferases except in the case of amino acid conjugation where the first step is catalyzed by an acyl CoA synthetase, then a transferase is involved. 

The taurine residue can also be found as an amide derivative of the 26-carboxylic acid function in the 3p,5a,6p,15a-polyhydroxylated steroids 328 and 329, which were obtained from the starfish Myxoderma platyacanthum [245]. The structures of both compounds were determined from spectral data and chemical correlations. The bile of the sunfish Mola mola has been shown to contain a new bile acid conjugated with taurine (330) together with sodium taurocholate. Compound 330 was identified as sodium 2-[3a,7a, 11 a-trihydroxy-24-oxo-5P-cholan-24-yl]amino]ethane-sulfonate on the basis of its physicochemical data and chemical transformations [246]. 

The second type involves the activation of the xenobiotic to form an acyl CoA derivative, which then reacts with an amino acid to form an amino acid conjugate. 

The conjugation of carboxylic acid xenobiotics with amino acids occurs in both liver and kidney and is catalyzed by an enzyme system located in the mitochondria. Conjugation requires initial activation of the xenobiotic to a Co A derivative in a reaction catalyzed by acyl CoA ligase. The acyl CoA subsequently reacts with an amino acid, giving rise to acylated amino acid conjugate and CoA. 

Amino acid conjugation has been reported to occur with glycine, glutamine, arginine, and taurine in mammals and certain primates. In other organisms, different amino acid acceptors are utilized in peptide conjugation. Ornithine is utilized by... 

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