Abstract
The two mammalian cyclooxygenase isoforms, COX-1 and COX-2, catalyze an identical reaction in the formation of prostaglandin H2 from arachidonic acid (Smith et al., 1996). The initial abstraction of the pro-S hydrogen at carbon C-13 is followed by oxygenation in the 11R position, formation of the endoperoxide and the five-membered prostaglandin ring, and, finally, a second oxygenation at C-15 to yield prostaglandin H2 (Hamberg and Samuelsson, 1967a).
As with all cyclooxygenases and lipoxygenases investigated so far, this mechanism follows the so-called antarafacial rule of hydrogen abstraction and oxygen insertion: both events occur on opposite sites of the planar cis,cis-pentadiene system of arachidonic acid (Hamberg and Samuelsson, 1967a; 1967b). COX-1 and COX-2, however, are different in their response to treatment with the non-steroidal anti-inflammatory drug, aspirin. In both enzymes, aspirin acetylates a critical serine residue in the active site channel. This leads to a complete block of oxygenase activity in COX-1, but to a new oxygenase specificity in COX-2, namely, formation of 15R-hydroxyeicosatetraenoic acid (15R-HETE) as the sole enzymatic product (Holtzman et al., 1992; Meade et al., 1993; Lecomte et al., 1994).
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Schneider, C., Boeglin, W.E., Brash, A.R. (2002). Analysis of Cyclooxygenase-Substrate Interactions Using Stereospecificallylabeled Arachidonic Acids. In: Honn, K.V., Marnett, L.J., Nigam, S., Dennis, E., Serhan, C. (eds) Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury, 5. Advances in Experimental Medicine and Biology, vol 507. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0193-0_8
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