Leukotrienes

The lipoxygenase enzymes are based in the cytosol of the lung, platelets and leukocytes. They convert arachidonic acid into hydroperoxy derivatives termed leukotrienes. The triggers for production are varied e.g. antigen binding in association with IgE in mast cells, activation of platelets. Leukotrienes are produced only when required.

The steps in production include:

• conversion of arachidonic acid to 5-hydroperoxyeicosatetraenoic acid, 5-HPETE, by the enzyme 5-lipoxygenase
• conversion of 5-HPETE to hydroxyeicosatetraenoic acid, HETE, by glutathione peroxidase
• or, coversion of 5-HPETE to leukotriene A4, LTA4, by the action of dehydrase enzymes

LTA4 then forms the basis for the production of further leukotrienes:

• leukotriene B4, LTB4, is formed by the action of a hydrolase predominantly in neutrophils
• leukotriene C4, LTC4, is formed by the action of a glutathione transferse enzyme in a range of cells

LTC4 may be futher enzymatically converted to leukotrienes D4 and E4, LTD4 and LTE4 respectively, by amino acid substitution.