The enzymology of human eicosanoid pathways: the lipoxygenase branches
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REVIEW
The enzymology of human eicosanoid pathways: the lipoxygenase branches Roger Gregory Biringer1 Received: 22 May 2020 / Accepted: 26 July 2020 © Springer Nature B.V. 2020
Abstract Eicosanoids are short-lived derivatives of polyunsaturated fatty acids that serve as autocrine and paracrine signaling molecules. They are involved numerous biological processes of both the well state and disease states. A thorough understanding of the progression the disease state and homeostasis of the well state requires a complete evaluation of the systems involved. This review examines the enzymology for the enzymes involved in the production of eicosanoids along the lipoxygenase branches of the eicosanoid pathways with particular emphasis on those derived from arachidonic acid. The enzymatic parameters, protocols to measure them, and proposed catalytic mechanisms are presented in detail. Keywords HETE · Eoxin · Hepoxilin · Trioxilin · Leukotriene · Lipoxin
Introduction Eicosanoids are amphipathic, signaling molecules produced by the oxidation of polyunsaturated fatty acids (PUFAs). In order to keep the scope within reasonable bounds, this review focusses primarily on eicosanoids derived from arachidonic acid (AA). These molecules are involved in numerous biological roles ranging from homeostasis of blood pressure and blood flow, to the perception of pain, cell survival the initiation and resolution of inflammation, and the progression of numerous disease states. These molecules are typically short-lived paracrine or autocrine signaling agents. A comprehensive description of the entire eicosanoid metabolic pathway would be a vast undertaking and is well beyond the scope of this review. For this reason, this manuscript is limited to those pathways involving lipoxygenase enzymes. Specifically, those involving the synthesis of hydroxyeicosatetraenoic acids (HETEs), lipoxins, hepoxilins, trioxillins and leukotrienes as well as a brief description Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11033-020-05698-8) contains supplementary material, which is available to authorized users. * Roger Gregory Biringer [email protected] 1
College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA
of resolvins, maresins, and protectins. Some major aspects not included in this review are pathways involving the epoxyeicosatrienoic acids and their cytochrome enzymes, prostanoid synthesis, and additional details on the metabolism of PUFAs beyond AA. In addition, the vast collection of resolvins, maresins, and protectins are only given a cursory look. This manuscript provides the basic elements of enzyme structure, assay protocols, kinetic parameters, and proposed mechanisms for many of the enzymes involved in the lipoxygenase pathways of eicosanoid metabolism.
Lipoxygenases In their classical role, Iipoxygenases represent a group of enzymes involved in the synthesis of wide range of derivatives of polyunsaturated fatty acids (PUFA) (Fig. 1). P
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