Carboxylic acids xenobiotic

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. 

Spahn, H. Langguth, P. Chiral amines derived from 2-arylpropionic acids novel reagents for the liquid chromatographic (LC) fluorescence assay of optically active carboxylic acid xenobiotics. Pharm.Res., 1990, 7, 1262-1268... 

The application of substrates isotopically labeled in specific positions makes it possible to follow the fate of individual atoms during the microbial degradation of xenobiotics. Under optimal conditions, both the kinetics of the degradation, and the formation of metabolites may be followed— ideally when samples of the labeled metabolites are available. Many of the classical studies on the microbial metabolism of carbohydrates, carboxylic acids, and amino acids used radioactive... 

MnP is the most commonly widespread of the class II peroxidases [72, 73], It catalyzes a PLC -dependent oxidation of Mn2+ to Mn3+. The catalytic cycle is initiated by binding of H2O2 or an organic peroxide to the native ferric enzyme and formation of an iron-peroxide complex the Mn3+ ions finally produced after subsequent electron transfers are stabilized via chelation with organic acids like oxalate, malonate, malate, tartrate or lactate [74], The chelates of Mn3+ with carboxylic acids cause one-electron oxidation of various substrates thus, chelates and carboxylic acids can react with each other to form alkyl radicals, which after several reactions result in the production of other radicals. These final radicals are the source of autocataly tic ally produced peroxides and are used by MnP in the absence of H2O2. The versatile oxidative capacity of MnP is apparently due to the chelated Mn3+ ions, which act as diffusible redox-mediator and attacking, non-specifically, phenolic compounds such as biopolymers, milled wood, humic substances and several xenobiotics [72, 75, 76]. 

The likelihood that a xenobiotic species will undergo enzymatic metabolism in the body depends on the chemical nature of the species. Compounds with a high degree of polarity, such as relatively ionizable carboxylic acids, are less likely to enter the body system and, when they do, tend to be quickly excreted. Therefore, such compounds are unavailable, or available for only a short time, for enzymatic metabolism. Volatile compounds, such as dichloromethane or diethylether, are... 

Foreign carboxylic acids and amines undergo biological acylation to form amide conjugates. Acylation reactions are of two types. The first involves an activated conjugating intermediate, acetyl CoA, and the xenobiotic. The reaction is referred to as acetylation. 

Several types of xenobiotic carboxylic acids (aromatic, heteroaromatic, arylacetic, and aryloxyacetic) are conjugated with a variety of endogenous amino... 

Conjugation with amino acids is an important route of Phase 2 metabolism for xenobiotics containing a carboxylic acid functional group. The amino acids involved include glycine, glutamine and taurine (an aminosulfonic... 

Many xenobiotic carboxylic acids undergo conjugation with one of a variety of amino acids. In which the carboxyl group of the xenobiotic Is linked In an amide (peptide) bound with the alpha-amino group of the amino acid (78). The chemical classes of acid Involved In amino acid conjugation are relatively few In number, and the reactions are restricted to certain aliphatic, aromatic, heteroaromatic, cinnamic and arylacetlc acids (28). The occurrence of the reaction Is markedly dependent on the steric hindrance around the carboxyl group by substituents on the aryl moiety or the side chain bearing the acid function (79). 

Xenobiotic carboxylic acids can be excreted as amino acid conjugates, where the COOH grot ) forms an amide bond with the -NHg group of an amino acid. In mammals, the aminn acid most commonly used for conjugation is glycine. This pathway has been studied in vitro and In vivo in several fish species and a marine Invertebrate. 

In several fish species and one marine crustacean, taurine conjugates of xenobiotic carboxylic acids have been Isolated from urine (fish) or hepatopancreas (Crustacea) and subjected to unequivocal chemical characterization (77-82). Table VIZ shows which acids are conjugated with taurine in some marine species. 

Although, as already discussed, aromatic carboxylic acids can be excreted as ester glucosides by many organisms, the major alternative mechanism for metabolizing such xenobiotics is through conjugation with an amino acid. 

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