Hydroperoxide isomerase

In plant tissues, various enzymes convert the hydroperoxides produced by LOX to other products, some of which are important as flavor compounds. These enzymes include hydroperoxide lyase, which catalyzes the formation of aldehydes and oxo acids hydroperoxide-dependent peroxygenase and epoxygenase, which catalyze the formation of epoxy and hydroxy fatty acids, and hydroperoxide isomerase, which catalyzes the formation of epoxyhydroxy fatty acids and trihydroxy fatty acids. LOX produces flavor volatiles similar to those produced during autoxidation, although the relative proportions of the products may vary widely, depending on the specificity of the enzyme and the reaction conditions. 

This enzyme [EC 4.2.1.92], also called hydroperoxide dehydratase and hydroperoxide isomerase, catalyzes the... 

Brodowsky, I. D., Hamberg, M., and Oliw, E. H. 1992. A Linoleic-Acid (8r)-Dioxy-genase and Hydroperoxide Isomerase of the Fungus Gaeumannomyces-Graminis. Biosynthesis of (8r)-Hydroxylinoleic Acid and (7s,8s)-Dihydroxylinoleic Acid from (8r)-Hydroperoxylinoleic Acid. J. Biol. Chem., 267, 4738-14745. 

Scheme 1.3. Hydroperoxide isomerase activity of cytochrome P450 is intramolecular.

Kupfer et al. have used this P450-hydroperoxide isomerase reaction to explore substrate mobility at the enzyme active site during the hydroxylation event. Isomerase substrates were found to remain in proximity to the P450 oxoferryl intermediate and were rapidly captured by the oxidant with high efficiency. Monooxygenase substrates, by contrast, apparently bind to ferric P450 in multiple orientations and undergo more extensive substrate reorientation prior to oxidative attack. This... 

Kupfer, R., S.Y. Liu, A.J. Allentoff, and J.A. Thompson (2001). Comparisons of hydroperoxide isomerase and monooxygenase activities of cytochrome P450 for conversions of allylic hydroperoxides and alcohols to epoxyalcohols and diols Probing substrate reorientation in the active site. Biochemistry 40, 11490-11501. 

In cereals the cleaving enzyme E2 is transformed into a hydroperoxid-isomerase and into a hydroperoxid cyclase producing prostaglandine-like components. 

Flaxseed contains a hydroperoxide isomerase converting the 13-hydroperoxide from linolenic acid to 13-hydroxy-12-oxo-18 2( 9, 15), 12-oxo-lO,15-phytodienoic acid (56) and some 9-hydroxy-12-oxo-18 2(10,15). The 9-hydroperoxide furnishes 9-hydroxy-lO-oxo-18 2(12,15) and some 13-hydroxy-10-oxo-18 2(115,15z).The... 

Recently, it has been shown that H-oxo-cm-IO, 15-phytodienoic acid is formed when a-linolenic acid is incubated with an extract of flaxseed powder in the presence of molecular oxygen (Zimmerman and Feng, 1978 Vick et al., 1979). Initially, the action of a lipoxygenase leads to formation of the well-known 13-L-hydroxyperoxy-cij, cis-9, 15-tra/is-ll-octatrienoic acid, a portion of which is converted by hydroperoxide isomerase to an a-ketol, whereas another portion is cyclized, through enzymatic action, to the 0x0-phytodienoic acid mentioned above (Vick and Zimmerman, 1979b). The sequence of reactions leading to this cyclic fatty acid is shown in Fig. 8. 

Jerneren F, Garscha U, Hoffmann I, Hamberg M, Oliw EH (2010) Reaction mechanism of 5,8-lino-leate diol synthase, lOR-dioxygenase, and 8,11-hydroperoxide isomerase of Aspergillus clavatus. Biochim Biophys Acta 1801 503-507... 

In addition to these pathways, several types of hydroperoxide isomerase reactions have been described [59],... 

More than 30 years ago it was reported that flaxseed homogenates convert 13-HpOTrE into a- and -y-ketols, and the enzyme responsible for this reaction was called hydroperoxide isomerase [54]. Later studies indicated that this reaction was actually a two-step process, consisting of an enzyme-catalysed dehydration of the hydroperoxy fatty acid to a rather unstable allene oxide followed by a non-enzymic hydrolysis [55,56]. The enzyme responsible for allene oxide synthesis has been purified and shown to be a cyt E-450 isoform [57]. As an alternative to hydrolysis, the allene oxide may undergo enzymic cyclization forming 12-oxo-phytodienoic acid. This compound is subsequently converted into jasmonic acid, a phytohormone implicated in the reaction of higher plants to a number of stimuli, such as wounding, fungal elicitation, mechanical forces and osmotic stress [54]. 

Hydroperoxide isomerase was the first enzyme discovered that used the hydroperoxide product of lipoxygenase as its substrate, the products being a-and Y-ketols (14,15). The 13-hydroperoxide isomer of llnolelc or linolenic acid is converted to both 13-hydroxy-12-oxo and 9-hydroxy-12-oxo products (Fig. 2), in approximately a 4 1 ratio, respectively. From the 9-hydroper-oxlde isomer, 9-hydroxy-lO-oxo and 13-hydroxy-10-oxo products are formed. 

Figure 4. Major fatty acid oxygenase pathways - lipoxygenase, hydroperoxide isomerase and lipoxins. Adapted from (37).

In barley grains, lipoxygenase has been well characterized and two isoenzymes have been purified [1-3] but the characterization of hydroperoxide-metabolizing enzymes has received less attention. Hydroperoxide-consuming enzymes can be divided into two types of enzymes. Hydroperoxide lyase cleaves fatty acid hydroperoxides into aldehydes and oxoacids, and hydroperoxide dehydrase (also named hydroperoxide isomerase) catalyzes the formation of a-and 7-ketols. 

Zimmerman DC, Vick BA. Hydroperoxide isomerase. A new enzyme of lipid metabolism. Plant Physiol 1979 53 1-4. 

Schwarz PB, Pyler RE. Lipoxygenase and hydroperoxide isomerase activity of malting barley. 

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