Mammalian lipoxygenases and their biological relevance

By H. Kuhn, Swathi Banthiya, K. van Leyen. Biochimica et Biophysica Acta, 2014

599 citations recorded by the source corpus.

Lipoxygenases (LOXs) form a heterogeneous class of lipid peroxidizing enzymes, which have been implicated in cell proliferation and differentiation but also in the pathogenesis of various diseases with major public health relevance. As other fatty acid dioxygenases LOX oxidize polyunsaturated fatty acids to their corresponding hydroperoxy derivatives, which are further transformed to bioactive lipid mediators (eicosanoids and related substances). On the other hand, lipoxygenases are key players in regulation of the cellular redox homeostasis, which is an important element in gene expression regulation. Although the first mammalian lipoxygenases were discovered 40 years ago and although the enzymes have been well characterized with respect to their structural and functional properties the biological roles of the different lipoxygenase isoforms are not completely understood. This review is aimed at summarizing the current knowledge on the physiological roles of different mammalian LOX-isoforms and their patho-physiological function in inflammatory, metabolic, hyperproliferative, neurodegenerative and infectious disorders.

Subfields: Biochemistry, Molecular Biology, Pharmacology

View Paper: https://www.semanticscholar.org/paper/1ab4dcb062617ae8377bbc41713d604422f3b62c

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In Biochemistry

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Citations in the corpus

• Advances in Our Understanding of Oxylipins Derived from Dietary PUFAs. (2015, methodology): “An alternative nomenclature is to use the gene names to describe the LOX enzymes (15).”
• Ferroptosis: mechanisms and links with diseases (2021, background): “The preferred substrate of Lox is free PUFAs, so the first step for Lox is to cleave PUFA acyl chains from PLs through the activity of phospholipase.(79) However, this model is inconsistent with ferroptosis, where the lipid peroxidation in ferroptosis occurs on esterified PUFA-PLs rather than free t”
• Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease. (2017, unknown): “Indeed, genetic depletion of LOXs protects against erastin-induced ferroptosis (Yang et al., 2016), suggesting LOXs contribute to ferroptosis.”
• Ferroptosis in cancer therapy: a novel approach to reversing drug resistance (2022, background): “In addition, several LOXs have been reported to be able to oxygenate PUFAs directly in a nonenzymatic way, thereby mediating ferroptosis [49].”
• Mechanisms of ferroptosis (2016, background): “The iron-dependent LOX enzymes catalyze site-specific oxidation of PUFAs such as AA, and are directly inactivated by lipo-philic iron chelators [58–60].”
• Reactive Oxygen Species-Induced Lipid Peroxidation in Apoptosis, Autophagy, and Ferroptosis (2019, background): “Arachidonic (C20: 4) and linoleic (C18: 2) are the most abundant polyenoic fatty acids that serve as substrates for LOX using molecular oxygen to form hydroperoxyl groups at different carbon position of acyl chains [40].”