The Enzymatic Formation of Novel Bile Acid Primary Amides
| Autor: | Marion Kirk, Kathleen A. Merkler, Uta Glufke, Lawrence King, John C. Vederas, Benjamin J. Wilcox, David J. Merkler, Stephen Barnes, Matthias E. Henz |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
medicine.drug_class
Stereochemistry Glycine Biophysics Glyoxylate cycle Biochemistry Mixed Function Oxygenases Substrate Specificity Bile Acids and Salts chemistry.chemical_compound Oxygen Consumption Multienzyme Complexes Amide medicine Bifunctional Molecular Biology chemistry.chemical_classification Bile acid Chemistry Glyoxylates Monooxygenase Kinetics Enzyme Heteronuclear molecule Oligopeptides Conjugate |
| Zdroj: | Archives of Biochemistry and Biophysics. 374:107-117 |
| ISSN: | 0003-9861 |
| DOI: | 10.1006/abbi.1999.1611 |
| Popis: | Bifunctional peptidylglycine α-amidating monooxygenase (PAM) catalyzes the copper-, ascorbate-, and O 2 -dependent cleavage of C-terminal glycine-extended peptides and N -acylglycines to the corresponding amides and glyoxylate. The α-amidated peptides and the long-chain acylamides are hormones in humans and other mammals. Bile acid glycine conjugates are also substrates for PAM leading to the formation of bile acid amides. The ( V MAX / K m ) app values for the bile acid glycine conjugates are comparable to other known PAM substrates. The highest ( V MAX / K m ) app value, 3.1 ± 0.12 × 10 5 M −1 s −1 for 3-sulfolithocholylglycine, is 6.7-fold higher than that for d -Tyr–Val–Gly, a representative peptide substrate. The time course for O 2 consumption and glyoxylate production indicates that bile acid glycine conjugate amidation is a two-step reaction. The bile acid glycine conjugate is first converted to an N -bile acyl-α-hydroxyglycine intermediate which is ultimately dealkylated to the bile acid amide and glyoxylate. The enzymatically produced bile acid amides and the carbinolamide intermediates were characterized by mass spectrometry and two-dimensional 1 H– 13 C heteronuclear multiple quantum coherence NMR. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect