5-Lipoxygenase discovery

Hamberg, M., C. Su, and E. Oliw, Manganese Lipoxygenase. Discovery of a his-Allylic Hydroperoxide as Product and Intermediate in a Lipoxygenase Reaction, /. Biol. Chem. 273 13080-13088 (1998). 

Lipoxygenase AnalytiCon Discovery db, Similarity based on 2D CATS descriptors 18 hits/430 tested [68]... 

Privett et al 123) made an important discovery in elucidating the structure of the products of the lipoxygenase reaction. They established... 

It is clear that 5-lipoxygenase (5-LO) [EC 1.13.11.34], through a two-step process, is the enzyme responsible for the production of LTA4. Thus the mechanism of action and, to a lesser extent, the structure of 5-LO have largely influenced the design and discovery of inhibitors of leukotriene biosynthesis. This enzyme has been the subject of intense research since its discovery, as discussed below (Section 5.1), and many inhibitors have been described. 

The leukotrienes, a family of compounds derived from the oxidative metabolism of arachidonic acid, have attracted the attention of a large portion of the scientific community in recent years. This present chapter deals primarily with the different chemical aspects associated with this field of research, in particular, their discovery their biogenesis, the strategic considerations envisaged in their synthesis, and the syntheses of the products associated with the 5-, 8-, 9-, 11-, 12-, and 15-lipoxygenase cascades. The literature to mid-1985 is covered. ... 

Brash AR, Boeglin WE, Chang MS. Discovery of a second 15S-lipoxygenase in humans. Proc Natl Acad Sci U S A. 94 (1997) 6148-6152. 

An obvious way to find out about the physiological function of an enzyme is to study the fate of the products that result from the reaction catalysed by the enzyme. The primary products of the lipoxygenase reaction, fatty-acid hydroperoxides, are potentially dangerous and should be quickly metabolized. Two major routes for metabolizing lipoxygenase products have been identified, collectively known as the lipoxygenase pathway [176]. This was recently extended by the discovery of the peroxygenase cascade [177]. 

Fatty acid hydroperoxides generated by plant lipoxygenases from linoleic and linolenic acids are known to serve as substrates for a divinyl ether synthase which produces divinyl ether fatty acids. Up to date divinyl ethers were detected only within the plant kingdom. The discovery of that class of compounds dates back to 1972, when the structures of two ether C18 fatty acids generated by homogenates of the potato tuber wee described. These compounds, named colneleic acid (from linoleic acid) and colnelenicacid (from linolenic acid), could be also produced in potato leaves and tomato roots by rearrangement of 9-hydroperoxides. 

After more than fifty years since its discovery, the study of the lipoxygenase pathway remains one of the most engaging, yet elusive areas of plant lipid research. Since 1932 when Andre and Hou (1) first reported on the existence of oxidizing enzymes which alter soybean oil. Chemical Abstracts has cited more than 1000 research articles under the subject of plant lipoxygenase. Despite the abundance of research effort on this topic, reviews (2-6) over the decades have been forced to report that the physiological role of lipoxygenase in plants is unknown. 

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