Cyclooxygenase catalytic mechanism

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.

The third folding unit is the catalytic domain of about 450 amino acid residues in length. The catalytic domain is encoded by the fifth to eleventh exons of the COX-1 gene or by the fourth to the tenth exons of the COX-2 gene. As described above, COX has two catalytic activities cyclooxygenase and peroxidase activity. The domain carries the active sites for the two functions. Fig. 8 shows a proposed scheme for the catalytic mechanism to explain the relationship between the two activities [59,60]. The secondary structure of the catalytic domain is predominantly a-helical with very little -sheet [48], The tertiary structure comprises two distinct lobes that are intertwined with each other (Fig. 9). The larger lobe is composed of seven helices (H2, H3, H5, H6, HIO, H18 and H19), while the smaller domain is... 

In this chapter the generation of free radicals, mainly superoxide and nitric oxide, catalyzed by prooxidant enzymes will be considered. Enzymes are apparently able to produce some other free radicals (for example, HO and N02), although their formation is not always rigorously proved or verified. The reactions of such enzymes as lipoxygenase and cyclooxygenase also proceed by free radical mechanism, but the free radicals formed are consumed in their catalytic cycles and probably not to be released outside. Therefore, these enzymes are considered separately in Chapter 26 dedicated to enzymatic lipid peroxidation. 

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