Leukotriene A₄ (LTA₄) is a

leukotriene Leukotrienes are a family of eicosanoid inflammation, inflammatory mediators produced in leukocytes by the redox, oxidation of arachidonic acid (AA) and the essential fatty acid eicosapentaenoic acid (EPA) by the enzyme arachidonate 5-lipoxyg ...

, and is the precursor for the productions of leukotriene B₄ (LTB₄) and leukotriene C₄ (LTC₄).

Biosynthesis

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 Arachidonate 5-lipoxygenase, also known as ALOX5, 5-lipoxygenase, 5-LOX, or 5-LO, is a non-heme iron-containing enzyme (EC 1.13.11.34) that in humans is encoded by the ''ALOX5'' gene. Arachidonate 5-lipoxygenase is a member of the lipoxygenase fa ...

(5-LO) and

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 ...

(FLAP) in the presence of ATP and

calcium ions Calcium ions (Ca2+) contribute to the physiology and biochemistry of organisms' cells. They play an important role in signal transduction pathways, where they act as a second messenger, in neurotransmitter release from neurons, in contraction ...

. The resulting 5-HPETE yields the unstable allylic epoxide substrate LTA₄ which is quickly hydrolyzed by the leukotriene A4 hydrolase (LTA₄H) enzyme to produce LTB₄, or synthesized by leukotriene C4 synthase (LTC₄S) with the addition of glutathione to produce LTC₄ which can be further metabolized to produce leukotriene D₄ (LTD₄) and leukotriene E₄ (LTE₄). 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

{{Leukotrienergics Eicosanoids