# Unusual and atypical cyclooxygenase reactions

## TL;DR

This paper explores unusual reactions of cyclooxygenase enzymes, revealing new prostaglandin analogs and biological activities from diverse fatty acid substrates.

## Contribution

The study identifies novel COX reactions and products, expanding understanding of COX's functional plasticity and catalytic mechanisms.

## Key findings

- COX enzymes can process fatty acids with 18 to 22 carbons and various chemical modifications.
- Stereochemistry at the 15-carbon changes in coral COX and COX-2 under aspirin treatment.
- COX's functional plasticity leads to the formation of new eicosanoids with unique biological activities.

## Abstract

Mechanistic studies have yielded novel prostaglandin analogs and acyclic products initially of interest in understanding cyclooxygenase (COX) structure and function, later found in vivo and of interest because of unique biological activities. Beyond arachidonic acid, fatty acid substrates span from 18 to 22 carbons and may contain ester/amide modification or epoxide/hydroxy moieties at the first double bond. Stereocontrol with the unconventional substrates remains largely intact although cyclization may be diverted or halted altogether, and catalysis proceeds with the insertion of one, two, or three molecules of oxygen into substrates. A switch in stereochemistry at the 15-carbon occurs in a natural COX from coral and has received attention upon aspirin treatment of COX-2. The latter produces 15R-hydroxyeicosatetraenoic acid and analogs from other fatty acids that may be further oxygenated by lipoxygenases. Functional plasticity in COX catalysis has enabled the formation and discovery of a host of novel eicosanoids and provided mechanistic insight into the COX reaction mechanisms.