Lipoxygenase products, role

Another group of 5-lipoxygenase products are the lipoxins LXA and LXB. Their biologic roles are still to be defined. 

GRF-stimulated GH release is also inhibited by lipoxygenase inhibitors, suggesting participation of some lipoxygenase product(s). However, in this area of research more work is also required to attribute a specific messenger role to these arachidonic acid metabolites. 

Galliard and Phillips 144) have found that homogenates of potato tubers contain an enzyme which converts the primary lipoxygenase product of linoleic acid, the 9-D-hydroperoxyoctadecadienoic acid, into an 18-carbon ether (Figure 3). Here too, cleavage of the Gig chain must occur. The formation and role of possible cleavage products from linoleic and linolenic acids in aroma and physiology of plant tissues have already been mentioned. 

Canonico PL, Speciale C, Sortino MA. Cronin MJ, MacLeo RM, Scapagnini U. Growth hormone releasing factor (GRF) increases free arachidonate levels in the pituitary a role for lipoxygenase products. Life Sci 1986 38 267-272. 

Israel E, Fischer A, Rosenberg M, et al. The pivotal role of 5-lipoxygenase products in the reaction of aspirin-sensitive asthmatics to aspirin. Am Rev Respir Dis 1993 148 1447-1451. 

AA is the substrate for most eicosanoid mediators produced by mammalian cells. It is also present in large amounts in phosphatidylinositol, a PL that functions in membrane signal transduction. The need for AA is probably the main reason why LA is essential for health. PUFA, especially of the n-3 type, are preferentially incorporated at the 2-position of most cell membrane PL and are considered to play an important role in both cell membrane integrity and function. Cellular stimulation leads to activation of phospholipase A, followed by mobilization of the FA on the 2-position of cell membrane PL. The types of these FA determine, to a great extent, the types of cyclooxygenase and lipoxygenase products. 

Antonipillai, I., Robin, E.C., Nadler, J.L. and Horton, R. (1986). Evidence for the inhibitory role of lipoxygenase products in renin release. Presented at the 6th International Conference on Prostaglandins and Related Compounds, June 3-6, Florence, Italy Whorton, A.R., Misono, K., Hollifield, J., Frolich, J.C., Inagami, T. and Oates, J.A. (1977). Prostaglandins and renin release from rabbit renal cortical slices by PGI2. Prostaglandins, 14, 1095-1104... 

POTENTIAL ROLE OF LIPOXYGENASE PRODUCTS IN ENDOTOXAEMIA AND ACUTE LUNG INJURY... 

The role of lipoxygenase in these events is still unknown. Mitogens cause release of arachidonic acid from the phospholipids [330] and generation of thromboxane Bj and lipoxygenase products [154]. Arachidonic acid, but not other fatty acids, stimulates blast transformation and incorporation of radiolabeled thymidine and uridine [331], and this effect is inhibited by lipoxygenase inhibition [232]. Thus, it is proposed that the lipoxygenase pathway produces factor(s) that promote mitogene-sis. 

Ikei, K. N., J. Yeung et al. 2012. Investigations of human platelet-type 12-hpoxygenase Role of lipoxygenase products in platelet activation, 53(12) 2546-2559. 

It has been reported that a single methionine residue of rabbit reticulocyte 15-lipoxygenase can be oxidized to its sulphoxide by treatment of the enzyme with 13-hydroperoxy-octadecadienoic acid (a 15-lipoxygenase product from linoleic acid) under anaerobic conditions [59]. Since under this condition the enzyme functioned as lipohydroperoxidase , splitting the hydroperoxide, and resulted in self-inactivation , a central role of the methionine residue was presumed for the catalysis of the enzyme. Recently, this particular methionine has been identified as Met-590 in human 15-lipoxygenase and as Met-591 in rabbit 15-lipoxygenase. When Met-590 in the human enzyme is replaced by leucine by the site-directed mutagenesis, the mutant enzyme is still inactivated by 13-hydroperoxyoctadeca-dienoic acid, 15-HpETE or AA. The result shows that the enzyme inactivation is not attributable to methionine oxidation [60]. 

Effects reminiscent of those described in Aplysia have been reported in vertebrate nervous systems. For example, a role for lipoxygenase products in modulating potassium M-type current has been suggested both in pyramidal neurons from the rat hippocampal formation and in neurons from the bullfrog sympathetic gan-glia 30-33 Moreover, in the rat hippocampus, 12-lipoxygenase products were also shown to inhibit the transient calcium rise and the release of glutamate elicited by membrane depolarization. ... 

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