title: Opioid peptides are substrates for the bifunctional enzyme LTA4 hydrolase/aminopeptidase.
abstract: We determined if any naturally occurring peptides could act as substrates or inhibitors of the bifunctional, Zn2+ metalloenzyme LTA4 hydrolase/aminopeptidase (E.C.3.3.2.6). Several opioid peptides including met5-enkephalin, leu5-enkephalin, dynorphin1-6, dynorphin1-7, and dynorphin1-8 competitively inhibited the hydrolysis of L-proline-p-nitroanilide by leukotriene A4 hydrolase/aminopeptidase, consistent with an interaction at its active site. The enzyme catalyzed the N-terminal hydrolysis of tyrosine from met5-enkephalin with Km = 450 +/- 58 microM and Vmax = 4.9 +/- 0.6 nmol-hr-1-ug-1 and from leu5-enkephalin with Km = 387 +/- 90 microM and Vmax = 6.2 +/- 2.5 nmol-hr-1-ug-1. Bestatin, captopril and carnosine inhibited the hydrolysis of the enkephalins. It is noteworthy that the bifunctional catalytic traits of this enzyme include generation of an hyperalgesic substance, LTB4, and inactivation of analgesic opioid peptides.
authors.affiliation: Department of Pharmacology, University of Colorado Health Science Center, Denver 80262.
authors.forename: K J
authors.initials: KJ
authors.lastname: Griffin
authors.forename: J
authors.initials: J
authors.lastname: Gierse
authors.forename: G
authors.initials: G
authors.lastname: Krivi
authors.forename: F A
authors.initials: FA
authors.lastname: Fitzpatrick
mesh_terms: D000595:Amino Acid Sequence; D002384:Catalysis; D004723:Endorphins / Q000502:physiology*; D004745:Enkephalins / Q000378:metabolism; D004851:Epoxide Hydrolases / Q000378:metabolism*; D006868:Hydrolysis; D007700:Kinetics; D008969:Molecular Sequence Data; D013379:Substrate Specificity
chemical_list: D004723:Endorphins; D004745:Enkephalins; D004851:Epoxide Hydrolases; C043134:leukotriene A4 hydrolase