Recognition and oxidative metabolism of cyclodipeptides by hepatic cytochrome P450
| Autor: | Christine Lamouroux, Christopher K. Jankowski, Marcel Delaforge, Maryse Jaouen, Geneviève Bouillé, Claude Bensoussan |
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| Rok vydání: | 2001 |
| Předmět: |
Male
Spectrometry Mass Electrospray Ionization Physiology Stereochemistry Peptide Endogeny Peptides Cyclic Biochemistry Rats Sprague-Dawley Cellular and Molecular Neuroscience Residue (chemistry) Dogs Endocrinology Cytochrome P-450 Enzyme System Animals Humans Chromatography High Pressure Liquid chemistry.chemical_classification Cytochrome P450 3A Binding Sites biology Hepatic cytochrome Active site Metabolism Rats Amino acid chemistry Microsomes Liver biology.protein Oxidation-Reduction |
| Zdroj: | Peptides. 22:557-565 |
| ISSN: | 0196-9781 |
| DOI: | 10.1016/s0196-9781(01)00364-3 |
| Popis: | Possible recognition of peptide derivatives by hepatic cytochrome P450 3A has been suggested by binding and metabolism of numerous pseudopeptidic compounds such as ergot derivatives and cyclosporin. Natural linear or cyclic dipeptides containing hydrophobic amino acids produced by microorganisms and present in mammals are able to interact with the P450 active site through either iron-amine interactions (Type II) or hydrophobic Type I interactions. P450 3A from dexamethasone-treated rats or yeast-expressed P450 human 3A4 are the most potent in such interactions, which are particularly strong with peptides containing a histidyl residue. Some cyclodipeptides are rapidly transformed by rat cytochrome P450 3A to mono- or dihydroxylated metabolites, with turnovers around 3 nmoles min −1 P450 −1 . Linear peptides are poorly transformed in these conditions. This metabolism of cyclodipeptides occurs in 8 species including man. Such interactions and metabolism have only minor consequences in terms of P450 3A binding and metabolism of classical P450 3A substrates. These data reinforce the concept that, in addition to their effect on the regulation of P450 neosynthesis, naturally occurring endogenous peptides are also substrates of P450 3A. The physiological activities of these peptides may be modulated by their metabolism. |
| Databáze: | OpenAIRE |
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