lipoxygenase pathway

Definition

Target type: biologicalprocess

The chemical reactions and pathways by which an unsaturated fatty acid (such as arachidonic acid or linolenic acid) is converted to other compounds, and in which the first step is hydroperoxide formation catalyzed by lipoxygenase. [GOC:mah, PMID:17163881]

The lipoxygenase pathway is a crucial metabolic route in various organisms, particularly animals and plants, responsible for the production of a diverse array of bioactive lipids. This pathway is initiated by the action of lipoxygenases (LOXs), a family of non-heme iron-containing dioxygenases that catalyze the oxygenation of polyunsaturated fatty acids, primarily arachidonic acid (AA). The following steps outline the lipoxygenase pathway:

1. **Substrate Binding and Oxygenation:** LOXs exhibit specificity for their substrates, typically polyunsaturated fatty acids with cis,cis-1,4-pentadiene structures. AA, a 20-carbon fatty acid with four double bonds, is a prominent substrate for LOXs. Upon binding to the enzyme, LOXs incorporate molecular oxygen into the substrate, forming a hydroperoxy intermediate.
2. **Formation of Hydroperoxyeicosatetraenoic Acids (HPETEs):** The hydroperoxy intermediate undergoes a series of enzymatic reactions, primarily catalyzed by different isoforms of LOXs, resulting in the production of various HPETEs. The specific HPETE formed depends on the LOX isoform involved and the position of the oxygenation within the fatty acid chain.
3. **Further Metabolism of HPETEs:** HPETEs are unstable intermediates and undergo further transformations. They can be reduced to hydroxyeicosatetraenoic acids (HETEs) by the action of peroxidases, or they can serve as precursors for the synthesis of other bioactive lipids.
4. **Production of Leukotrienes:** 5-lipoxygenase (5-LOX) is a key enzyme in the leukotriene biosynthesis pathway. It oxygenates AA at the 5-position, producing 5-HPETE. 5-HPETE is further converted to leukotriene A4 (LTA4), a highly reactive epoxide, and subsequently to various leukotrienes, including LTB4, LTC4, LTD4, and LTE4. Leukotrienes are potent inflammatory mediators, playing roles in chemotaxis, bronchoconstriction, and vascular permeability.
5. **Production of Lipoxins:** 12-LOX and 15-LOX can interact to produce lipoxins, a class of anti-inflammatory mediators. These enzymes catalyze the oxygenation of AA at the 12- and 15-positions, respectively. The resulting 12-HPETE and 15-HPETE can undergo enzymatic transformations to form lipoxins.
6. **Regulation of the Lipoxygenase Pathway:** The lipoxygenase pathway is tightly regulated by various factors, including cellular signaling pathways, transcription factors, and post-translational modifications. These mechanisms ensure appropriate production of lipoxygenase products in response to specific stimuli.

The lipoxygenase pathway plays a critical role in mediating various physiological and pathological processes. Its products, including leukotrienes, lipoxins, and HETEs, exert diverse biological effects, ranging from inflammation and immunity to vascular homeostasis and cell proliferation.'
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Proteins (11)

Compounds (1,121)