Glutathione, S-substituted glutathiones, and leukotriene C4 as substrates for peptidylglycine α-amidating monooxygenase (original) (raw)
2003, Archives of Biochemistry and Biophysics
The C-terminal a-amide moiety of most peptide hormones arises by the posttranslational cleavage of a glycine-extended precursor in a reaction catalyzed by bifunctional peptidylglycine a-amidating monooxygenase (PAM). Glutathione and the S-alkylated glutathiones have a C-terminal glycine and are, thus, potential substrates for PAM. The addition of PAM to glutathione, a series of S-alkylated glutathiones, and leukotriene C 4 results in the consumption of O 2 and the production of the corresponding amidated peptide and glyoxylate. This reaction proceeds in two steps with the intermediate formation of a C-terminal a-hydroxyglycineextended peptide. Amidated glutathione (cGlu-Cys-amide) is a relatively poor substrate for glutathione S-transferase with a V =K value that is 1.3% of that for glutathione. Peptide substrates containing a penultimate hydrophobic or sulfur-containing amino acid exhibit the highest ðV =KÞ app values for PAM-catalyzed amidation. The S-alkylated glutathiones incorporate both features in the penultimate position with S-decylglutathione having the highest (V =KÞ app of the substrates described in this report.
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