title: Oxidative metabolism of lipoamino acids and vanilloids by lipoxygenases and cyclooxygenases.
abstract: The lipoamino acids and endovanilloids have multiple roles in nociception, pain, and inflammation, yet their biological reactivity has not been fully characterized. Cyclooxygenases (COXs) and lipoxygenases (LOs) oxygenate polyunsaturated fatty acids to generate signaling molecules. The ability of COXs and LOs to oxygenate arachidonyl-derived lipoamino acids and vanilloids was investigated. COX-1 and COX-2 were able to minimally metabolize many of these species. However, the lipoamino acids were efficiently oxygenated by 12S- and 15S-LOs. The kinetics and products of oxygenation by LOs were characterized. Whereas 15S-LOs retained positional specificity of oxygenation with these novel substrates, platelet-type 12S-LO acted as a 12/15-LO. Fatty acid oxygenases may play an important role in the metabolic inactivation of lipoamino acids or vanilloids or may convert them to bioactive derivatives.
authors.affiliation: A. B. Hancock, Jr. Memorial Laboratory for Cancer Research, Vanderbilt Institute of Chemical Biology, and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Jeffery J
authors.initials: JJ
authors.lastname: Prusakiewicz
authors.forename: Melissa V
authors.initials: MV
authors.lastname: Turman
authors.forename: Andrew
authors.initials: A
authors.lastname: Vila
authors.forename: Heather L
authors.initials: HL
authors.lastname: Ball
authors.forename: Ahmad H
authors.initials: AH
authors.lastname: Al-Mestarihi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Marnett
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D051545:Cyclooxygenase 1 / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D006801:Humans; D008084:Lipoxygenase / Q000378:metabolism*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism*; D011817:Rabbits
chemical_list: D000596:Amino Acids; D008084:Lipoxygenase; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D010100:Oxygen