Glutathione, S-substituted glutathiones, and leukotriene C4 as substrates for peptidylglycine alpha-amidating monooxygenase.
The C-terminal alpha-amide moiety of most peptide hormones arises by the posttranslational cleavage of a glycine-extended precursor in a reaction catalyzed by bifunctional peptidylglycine alpha-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 alpha-hydroxyglycine-extended peptide. Amidated glutathione (gammaGlu-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 (V/K)(app) values for PAM-catalyzed amidation. The S-alkylated glutathiones incorporate both features in the penultimate position with S-decylglutathione having the highest (V/K)(app) of the substrates described in this report.
Miller
Laura Aaron
LA
Department of Chemistry, University of South Florida, Tampa, FL 33620, USA.
Baumgart
Laura E
LE
Chew
Geoffrey H
GH
deLong
Mitchell A
MA
Galloway
Lamar C
LC
Jung
Kyung Woon
KW
Merkler
Kathleen A
KA
Nagle
Advait S
AS
Poore
Derek D
DD
Yoon
Cheol Hwan
CH
Merkler
David J
DJ
D000596:Amino Acids / Q000737:chemistry; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000737:chemistry*; D005982:Glutathione Transferase / Q000378:metabolism; D006736:Horses; D006868:Hydrolysis; D007700:Kinetics; D017997:Leukotriene C4 / Q000737:chemistry*; D013058:Mass Spectrometry; D006899:Mixed Function Oxygenases / Q000737:chemistry*; D008956:Models, Chemical; D009097:Multienzyme Complexes / Q000737:chemistry*; D010100:Oxygen / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013997:Time Factors
D000596:Amino Acids; D009097:Multienzyme Complexes; D010455:Peptides; D017997:Leukotriene C4; D006899:Mixed Function Oxygenases; C035189:peptidylglycine monooxygenase; D005982:Glutathione Transferase; D005978:Glutathione; D010100:Oxygen