Hydroxyeicosatrienoic acids

GLA is metabolized to DGLA in neutrophils by the addition of two carbons. DGLA is metabolized to 15-hydroxyeicosatrienoic acid (Chilton-Lopez et al., 1996) by 5-lipoxygenase (Miller et al., 1990). 

Murphy, R.C., J.R. Falck, S. Lumin, P. Yadagiri, J.A. Zirrolli, M. Balazy et al. (1988). 12(S)-Hydroxyeicosatrienoic acid A vasodilator cytochrome P-450-dependent arachidonate metabolite from bovine comeal epithelium. J. Biol. Chem. 263, 17197-17202. 

Fig. 5. Metabolism of dietary linoleic acid (LA) and y-linolenic acid (GLA) in epidermis. Abbreviations DGLA, dihomo-y-linolenic acid AA, arachidonic acid 15-LOX, 15-lipoxyge-nase 13-HODE, 13-hydroxyoctadecadienoic COX, cyclooxygenase PGE, prostaglandin E, 15-HETrE, 15-hydroxyeicosatrienoic acid.

Fig. 6. Comparative effects of 135-hydroxyoctadecadienoic acid (135-HODE) and 15S-hydroxyeicosatrienoic acid (155-HETrE). Abbreviation DHA, docosahexaenoic acid.

Fig. 8. Suppression of docosahexaenoic acid (DHA)-induced expression of epidermal nuclear mitogen-activated protein kinase (MARK) by 15-hydroxyeicosatrienoic acid (15-HETrE) and 135-hydroxyoctadecadienoic acid (13S-HODE).

Fig. 9. Speculative scenario of nutrient y-linolenic acid (GLA)/linoleic acid (LA) modulation of nuclear transcription factor. Abbreviations 15-LOX, 15-lipoxygenase 15S-HETrE, 15S-hydroxyeicosatrienoic acid 13-HODE, 13-hydroxyoctadecadienoic PIP, phosphatidylinositol phosphate PKC, protein kinase C DAG, diacylglycerol MAPK, mitogen-activated protein kinase AP-1, activator protein 1.

Xi, S., Pham, H., and Ziboh, V.A. (2000) Suppression of Proto-Oncogene (AP-1) in a Model of Skin Epidermal Hyperproliferation Is Reversed by Topical Application of 13-Hy-droxyoctadecadienoic Acid and 15-Hydroxyeicosatrienoic Acid, Prostaglandins Leukot. Essent. Fatty Acids 62,13-19. 

Microsomal cytochrome P450 (CYP) monooxygenases are better known for their role in xenobiotic metabolism, a process which is crucial in the therapeutic and toxic effects associated with pharmaceuticals. However, they are also involved in the biosynthetic transformation of PUFA to epoxy-, mono-hydroxylated- and di-hydroxylated-metabolites. When AA is the substrate, CYP-reactions produce a range of epoxyeicosatrienoic acids (EET), hydroxyeicosatrienoic acids (HETE), and dihydroxyeicosatrienoic acids (DHET) (Eigure 3.5). 

Pham, H., T. Banerjee et al. 2004. Suppression of cyclooxygenase-2 overexpression by 15S-hydroxyeicosatrienoic acid in androgen-dependent prostatic adenocarcinoma cells. IntJ Canc 111(2) 192-197. 

Xi, S., H. Pham et al. 2000. Suppression of proto-oncogene (AP-1) in a model of skin epidermal hypeiproliferation is reversed by topical application of 13-hydroxyoctadecadienoic acid and 15-hydroxyeicosatrienoic acid. 

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