Leukotriene A4 (LTA4) is an inflammatory, unstable intermediate product of the 5-lipoxygenase metabolism of arachidonic acid. Leukotriene A4 (leukotriene: from ancient Greek λευκός leukós, "white" and τρεῖς, τρία treis, tría "three") is produced by neutrophil granulocytes and mononuclear phagocytes in response to inflammatory mediators.
The biological activities of LTA4 are essentially determined by its metabolites, in particular by LTB4 and by some cysteinyl leukotrienes (LTC4, LTD4, LTE4). Leukotriene A4 (LTA4) is the first metabolite in the reaction chain that leads to the synthesis of several leukotrienes.
The 5-lipoxygenase (5-LO) catalyzes the biotransformation of arachidonic acid to LTA4 in 2 steps. The first step in the synthesis of LTA4 consists of the oxidation of arachidonic acid to the unstable intermediate product 5-hydroperoxyeicosatetraenoic acid (5-HPETE). The 2nd step consists of the dehydration of 5-HPETE and the synthesis of LTA4.
All eicosanoids function locally around the site of synthesis. All bind to G-protein-bound transmembrane receptors. Human B and T lymphocytes produce leukotriene B4 when incubated with leukotriene A4. Furthermore, in humans erythrocytes, thrombocytes and keratinocytes as well as other cells are able to convert leukotriene A4 into leukotriene B4. The prerequisite for this conversion is the expression of the enzyme leukotriene A4 hydrolase (LTAH). Leukotriene A4 hydrolase (LTAH) is a bifunctional key enzyme that on the one hand hydrolyzes the unstable leukotriene A4 into leukotriene B4; on the other hand, the enzyme acts like an aminopeptidase.