Leukotriene A4
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Leukotriene A4 (LTA4) is a
leukotriene Leukotrienes are a family of eicosanoid inflammatory mediators produced in leukocytes by the oxidation of arachidonic acid (AA) and the essential fatty acid eicosapentaenoic acid (EPA) by the enzyme arachidonate 5-lipoxygenase. Leukotrienes ...
, and is the precursor for the productions of LTB4 (
leukotriene B Leukotrienes are a family of eicosanoid inflammatory mediators produced in leukocytes by the oxidation of arachidonic acid (AA) and the essential fatty acid eicosapentaenoic acid (EPA) by the enzyme arachidonate 5-lipoxygenase. Leukotrie ...
)) and LTC4 (
leukotriene C4 Leukotriene C4 (LTC4) is a leukotriene. LTC4 has been extensively studied in the context of allergy and asthma. In cells of myeloid origin such as mast cells, its biosynthesis is orchestrated by translocation to the nuclear envelope along with c ...
).


Biosynthesis of Leukotriene A4

Following the biosynthesis of eicosanoid, triggered as a result of infection or inflammation, the resulting arachidonic acid substrate is released from the cell membrane phospholipid will enter the lipooxygenase pathway to produce Leukotriene A4. In this pathway, arachidonic acid is converted into 5-hydroperoxyeicosatetraenoic acid (5-HPETE) as a result of a catalytic complex consisting of the enzyme 5-lipoxygenase (5-LO) and FLAP (
5-Lipoxygenase-activating protein Arachidonate 5-lipoxygenase-activating protein also known as 5-lipoxygenase activating protein, or FLAP, is a protein that in humans is encoded by the ''ALOX5AP'' gene. Function FLAP is necessary for the activation of 5-lipoxygenase and theref ...
) in the presence of ATP and Calcium ions. The resulting 5-HPETE yields the unstable allylic epoxide substrate LTA4 which is quickly hydrolyzed by the LTA4H (
Leukotriene A4 hydrolase Leukotriene A4 hydrolase, also known as LTA4H is a human gene. The protein encoded by this gene is a bifunctional enzyme () which converts leukotriene A4 to leukotriene B4 and acts as an aminopeptidase. Function This enzyme belongs to the fami ...
) enzyme to produce LTB4, or synthesized by LTC4S (
Leukotriene C4 synthase Leukotriene C4 synthase is an enzyme that in humans is encoded by the ''LTC4S'' gene. The protein encoded by this gene, LTC4S (or glutathione S-transferase II) is an enzyme that converts leukotriene A4 and glutathione to create leukotriene C4. Th ...
) with the addition of glutathione to produce LTC4 which can be further metabolized to produce LTD4 (
Leukotriene D4 Leukotriene D4 (LTD4) is one of the leukotrienes. Its main function in the body is to induce the contraction of smooth muscle, resulting in bronchoconstriction and vasoconstriction. It also increases vascular permeability. LTD4 is released by bas ...
) and LTE4 (
Leukotriene E4 Leukotriene E4 (LTE4) is a cysteinyl leukotriene involved in inflammation. It is known to be produced by several types of white blood cells, including eosinophils, mast cells, tissue macrophages, and basophils, and recently was also found to be pr ...
). The lipooxygenase pathway is one of several possible pathways including the cyclooxygenase pathway (also PGH synthase pathway), isoprostane pathway, and cytochrome P450 epoxygenases pathway following the arachidonic acid metabolism, but is the only pathway in which the subsequent steps will lead to the production of leukotrienes.


References

Eicosanoids {{biochemistry-stub