Cysteine conjugation reactions

The principal mercapturic acid derivative, N-acetyl-S-(2-hydroxyethyl-)L-cysteine, and other related metabolites are derived from the conjugation reaction of 1,2-dibromoethane with glutathione, a molecule present in mammalian cells. This suggests that the primary pathway of... 

Evidence was also provided that Insoluble residues may be produced from GSH conjugates via cysteine conjugate or thiol Intermediates. These studies also suggested that certain reactions should be studied in greater detail to assess their importance in pesticide metabolism l.e., the C-S lyase reaction, the methyl transferase reaction, and the transamination reaction. 

The sulfate molecule used in conjugation reactions is derived from 3-phosphoadenosine-5 -phosphosulfate (PAPS). Efficient synthesis of PAPS requires an adequate amount of inorganic sulfate with L-cysteine, D-cysteine, or L-methionine serving as precursors for the inorganic sulfate. PAPS is likely synthesized in every vertebrate cell, with high concentrations produced in the liver. 

Alternatively, R-cysteine is utilized for the biosynthesis of cosubstrates for several conjugation reactions, such as glutathione, sulfate (PAPS), and taurine. The unphysiological isomer S-cysteine has been used to investigate the mechanistic aspects of physiological processes involving cysteine. In rats, the sulfoxidation rates of R- and S-cysteine, as well as the sulfation rates of the test substrate harmol sulfate, were found to be very similar, so that stereoselectivity for the amino acid does not seem to play a role in these reactions (Glazenburg et al., 1984). Since S-cysteine, in contrast to the R-isomer, did not increase the taurine concentration in serum, this type of stereoselectivity can be used to selectively enhance sulfate availability in vivo. 

The chemoselective Michael addition of sulfhydryl group to the maleimido group is a well-known conjugation reaction tmder neutral pH, which has been commonly used for the coupling of fiuorophores to proteins with surface-exposed cysteine residues. The reaction was used to conjugate a maleimidocaproyl (MIC) peptide to a C-terminally truncated Ras protein bearing a C-terminal cysteine (Scheme 12). 

GSH (because of the sulfhydryl group of its cysteine, which is the business part of the molecule). A number of potentially toxic electrophilic xenobiotics (such as certain carcinogens) are conjugated to the nucleophilic GSH in reactions that can be represented as follows ... 

The most significant amino acids for modification and conjugation purposes are the ones containing ionizable side chains aspartic acid, glutamic acid, lysine, arginine, cysteine, histidine, and tyrosine (Figure 1.6). In their unprotonated state, each of these side chains can be potent nucleophiles to engage in addition reactions (see the discussion on nucleophilicity below). 

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