Leukotria a4

Leukotriene A4 (LTA4) is an inflammatory, unstable intermediate of the 5-lipoxygenase metabolism of arachidonic acid. Leukotriene A4 (leukotriene: from Greek leukos =white and treis =three) is formed by neutrophilic granulocytes and mononuclear phagocytes in response to acting inflammatory mediators.

The biological activities of LTA4 are essentially determined by its metabolites, especially LTB4 and some cysteinyl leukotrienes (LTC4, LTD4, LTE4). Leukotriene A4 (LTA4) is the first metabolite in the reaction chain leading to the synthesis of several leukotrienes.

The 5-lipoxygenase (5-LO) catalyses the biotransformation of arachidonic acid to LTA4 in 2 steps. The first step in the synthesis of LTA4 is the oxidation of arachidonic acid to the unstable intermediate product 5-hydroperoxyeicosatetraenoic acid (5-HPETE). The second step consists in 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. In humans, erythrocytes as well as platelets, keratinocytes and other cells are able to convert leukotriene A4 into leukotriene B4. A prerequisite for this conversion is the expression of the enzyme leukotriene A4 hydrolase (LTAH). The leukotriene A4 hydrolase (LTAH) is a bifunctional key enzyme which on the one hand hydrolyses the unstable leukotriene A4 into leukotriene B4. On the other hand, the enzyme acts like an aminopeptidase.

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