Cyclooxygenase reaction

The mode of action of these compounds, which are under investigation, is via an antioxidative mechanism. Since COX enzyme catalysis involves radical intermediates, a radical scavenging moiety such as a di-fenf-butylphenol interferes with the cyclooxygenase reaction. Linkage of phenolic substructure with a thiazolone, oxazolone, thiadiazole or oxadiazole derivative produces non-... 

Several mechanisms have been proposed for the dioxygenation of arachidonic acid by PGHS (the cyclooxygenase reaction). The involvement of free radical intermediates derived from the abstraction of a hydrogen atom at position 13 of arachidonic acid was proposed [14], A mechanism deduced from that generally... 

Enzymatic assay of lipid hydroperoxides A selective assay has been described for lipid hydroperoxides, based on the cyclooxygenase reaction with a sensitivity in the range of 20-200 pmol (Marshall et al., 1985 Pendleton and Lands, 1987 Lands, 1988). The substrate (15-HPETE) is not, however, commercially available and must therefore be synthesized from purified arachidonic acid by the method of Graft (1982) in which soya bean lipoxygenase is used to catalyse the stereospecific oxygenation of arachidonic acid. 

Figure 12.6. Catalytic mechanism of the cyclooxygenase reaction, leading from arachidonic acid (top left) to prostaglandin G2 (top right). Y and YH represent Tyr 3 85. Molecular oxygen reacts in its jT-radical form. Note that this is only the first one of the two reactions catalyzed by cyclooxygenase.

Kiefer JR, Pawlitz JL, Moreland KT, Stegeman RA, Hood WF, Gierse JK, Stevens AM, Goodwin DC, Rowlinson SW, Marnett LJ, Stallings WC, Kummbail RG. Structural insights into the stereochemistry of the cyclooxygenase reaction. Nature 2000 405 97-101. 

Cyclooxygenase 1 (COX-1) is the common name used to describe the protein prostaglandin H synthase 1 (PGHS-1), which performs both peroxidase and cyclooxygenase reactions to make PGH, the precursor to prostaglandins E, D, F2 prostacyclin, and thromboxane A, (see Fig. 5.3). Originally described as an... 

Stegeman R, Pawlitz J, Stevens A, Gierse J, Stallings W, KurumbaU R (1998) Mechanism of cyclooxygenase reactions structure of arachidonic acid bound to cyclooxygenase-2. American Crystallographic Association. Abstract... 

El and ET cannot bind fatty acid and thus neither can catalyze the cyclooxygenase reaction. For aspirin, conversion of El to El is accompanied by covalent modification of the protein, making the transition irreversible. 

Fig. 3. Mechanism for the cyclooxygenase reaction showing the conversion of arachidonic acid and two molecules of oxygen to PGGj.

It has been suggested that a tyrosyl radical is generated in the peroxidase active site (on Y385 of COX-1) and is used to form an arachidonafe radical that reacts with O2 in the cyclooxygenase reaction. 266b Alternatively, a carbocation mechanism is also possible. ... 

The stoichiometry of the cyclooxygenase reaction has been investigated with an ovine microsomal preparation. A 1 2 ratio of fatty acid conversion and oxygen consumption was demonstrated [34,35]. The enzyme is saturated with 30 /xM oxygen, the for which is about 5 juM [36]. Either arachidonic acid or 8,11,14-eico-... 

Fig. 2. Hypothetical mechanism of fatty acid cyclooxygenase reactions.

Fig. 1. Proposed mechanisms for prostaglandin H. synthase. The holoenzyme catalyzes both the cyclooxygenase reaction (at the right) and the peroxidase reaction (at the left).

An interesting feature of the mangano-protoporphyrin analog of PGH synthase is its ability to perform cyclooxygenase reactions while providing no measurable peroxidase activity [13]. This finding has allowed study of the cyclooxygenase activity separate from that of the peroxidase [14] whereas both activities occur simultaneously when the enzyme is assisted by Fe protoporphyrin. 

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