Co‐Oxidation by Cyclooxygenases

Abstract

Cyclooxygenases (COXs; prostaglandin H(2) synthases) catalyze the bis-dioxygenation of arachidonic acid (AA) to generate prostaglandin (PG) G(2) followed by the peroxidative cleavage of PGG(2) to yield PGH(2), the precursor to all of the vasoactive PGs. These enzymes utilize a Fe-protoporhyrin IX (heme) co-factor to catalyze peroxide bond cleavage, which puts the Fe at a higher oxidation state (Fe(3+) → Fe(5+)). The heme Fe requires two electrons (e(-)) to return to its resting state (Fe(3+)) for the next round of catalysis. Peroxide bond cleavage thus occurs via compound I and compound II, observed for horseradish peroxidase. To return to Fe(3+), electrons come from "co-reductants" and their subsequent oxidation by the enzyme is known as "co-oxidation". The protocols in this unit are aimed at characterizing this side reaction of COXs.

CD64 and Group II Secretory Phospholipase A2 (sPLA2-IIA) as Biomarkers for Distinguishing Adult Sepsis and Bacterial Infections in the Emergency Department

“…The metabolism of arachidonic acid leads to the generation of arachidonic acid metabolites, catalyzed by various enzymes. All of these metabolites are pro-inflammatory mediators; they include 5-hydroperoxyeicosatetraenoic acid (HPETE, generated by activity of lipoxygenase) [ 19 , 20 ] and prostaglandin G2 [ 21 , 22 ] (catalyzed by cyclooxygenase). HPETE can be converted further into leukotrienes [ 23 ] and hydroxyicosatetraenoic acid (HETE) [ 24 ], while prostaglandin G2 can be catalyzed further to generate thromboxanes (thromboxane A2 and B2) [ 25 ], prostacyclin (PGI2) [ 26 ] and various forms of prostaglandins (prostaglandins D2, E2 and F2α) [ 27 ] which will further amplify the inflammation signals [ 28 – 31 ].…”