Enzymatic studies with 3-oxa n-3 DPA

Bioorg Chem. 2020 Mar;96:103653. doi: 10.1016/j.bioorg.2020.103653. Epub 2020 Feb 8.

Abstract

Cyclooxygenase-2 and several lipoxygenases convert polyunsaturated fatty acids into a large variety of products. During inflammatory processes, these enzymes form several distinct families of specialized pro-resolving lipid mediators possessing potent anti-inflammatory and pro-resolving effects. These mediators have attracted a great interest as leads in drug discovery and have recently been the subject of biosynthetic pathway studies using docosahexaenoic and n-3 docosapentaenoic acid as substrates. Herein we present enzymatic studies with cyclooxygenase-2 and 5-, 12- and 15-lipoxygenase enzymes using 3-oxa n-3 DPA as a synthetic mimic of n-3 docosapentaenoic acid. Structural elucidation based on data from RP-HPLC UV and LC/MS-MS experiments enabled the identification of novel enzymatically formed products. These findings constitute the basis for further biosynthetic studies towards understanding the mechanisms regulating substrate utilization in the biosynthesis of specialized pro-resolving lipid mediators.

Keywords: 3-oxa n-3 DPA; Biosynthesis; Cyclooxygenase-2; Lipids; Lipoxygenases; Oxygenated products; Polyunsaturated fatty acids; Specialized pro-resolving lipid mediators.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonate 12-Lipoxygenase / metabolism*
  • Arachidonate 15-Lipoxygenase / metabolism*
  • Arachidonate 5-Lipoxygenase / metabolism*
  • Cyclooxygenase 2 / metabolism*
  • Fatty Acids, Unsaturated / metabolism*
  • Humans
  • Mice
  • Soybeans / enzymology
  • Soybeans / metabolism
  • Substrate Specificity

Substances

  • Fatty Acids, Unsaturated
  • Arachidonate 12-Lipoxygenase
  • Arachidonate 15-Lipoxygenase
  • Arachidonate 5-Lipoxygenase
  • Cyclooxygenase 2
  • docosapentaenoic acid