Lipoxygenase nonheme iron

Veldink, G. A., and Vliegenthart, J. F. 1984. Lipoxygenases, nonheme iron-containing enzymes. Adv. Inorg. Biochem., 6,139-161. 

Lipoxygenase (EC 1.13.11.12, nonheme iron dioxygenase), the substrate (polyunsaturated fatty acid) is poorly water soluble and the product (hydroperoxy-fatty acid) is hydrophilic. The reaction occurs in the aqueous phase [85,86]. 

Iron-containing superoxide dismutases are present in many species of bacteria (Hassan and Fridovitch, 1978). These nonheme iron proteins have a characteristic set of EPR lines split about g = 4.2 in the ferric state, arising from the middle Kramers doublet of a rhombic high-spin site. Ferrous iron superoxide dismutase forms an S = I complex with NO that resembles the lipoxygenase-NO adduct by EPR criteria (I. Fridovich, T. Kirby, and J. C. Salerno, (1978) unpublished observations). 

These results indicate that the Fusarium lipoxygenase differs from the soybean lipoxygenase in various respects soybean lipoxygenase is a nonheme iron-containing dioxygenase and has a molecular weight of 102,000, optimum pH of 6.5 to 7,0 and isoelectric point of pH 5.4. The soybean enzyme is not inhibited by cyanide and catalyzes the peroxidation of linoleic acid and linolenic acid at equal rates74-76,193. ... 

The committed biosynthetic path to the leukotrienes begins (see Fig. 5.2) with the action of 5-lipoxygenase (5-LO)[EC 1.13.11.34] (14)on arachidonic acid. Purified human 5-LO is an unstable, 78,000-Da protein that has been isolated and cloned (15,16). It contains a tightly bound, nonheme iron that is essential for enzymatic activity (17). Like all known lipoxygenases, 5-LO catalyzes the insertion of molecular oxygen into a l,4-cis,cis-pentadiene unit. The effect of 5-LO on AA is to abstract stereospecifically the pro-S hydrogen at position C7 and to insert molecular oxygen at... 

Interestingly, even at that time, a series of five histidine residues was postulated to constitute the potential iron-binding site, in that they are also conserved in other lipoxygenases, although site-specific mutagenesis studies indicated that three of these could be mutated individually in 5-LO without loss of either oxygenase or LTA4 synthetase activity (112,113). This proposal has now been refined and it is believed that the nonheme iron is bound permanently by and... 

Lipoxygenases (LOs) are nonheme, mononuclear iron enzymes that catalyze the regio- and stereoselective conversion of polyunsaturated fatty acids with a di.di-1,4-diene functionality into products having a l-hydroperoxy-tra 5, cM-2,4-diene functionality. The mammalian LOs typically act on arachidonic acid and produce alkyl hydroperoxides that are converted into leukotrienes and lipoxins, which are involved as messengers in the inflammatory response. Plant enzymes act on linoleic acid, but the role of the product alkyl hydroperoxide is less well understood. 

Iron-containing enzymes are attributed either to the heme (examples in 3.3.2.2) or to the nonheme Fe-containing proteins. The latter case is exemplified by lipoxygenase, for which the mechanism of activity is illustrated in section 3.7.2.2, or by xanthine oxidase. 

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