Leukotriene are synthesized mostly in of myeloid origin cells, like basophils, eosinophils, macrophages, monocytes, stem cells...
The initial step in the synthesis of leukotrienes is the cleavage of an arachidonoyl ester bond of a glycerophospholipid through the action of a PLA2 in a hydrolysis reaction that yields lysophospholipid and free arachidonic acid. Cellular levels of arachidonic acid and lysophospholipid are tightly regulated; one of the main mechanism that the cell use to mantain the right equilibrium is the so called Lands cycle. In this cycle arachidonic acid is conjugated with CoA through an acyl-CoA ligase and then is esterified to a lysophospholipid by a LAT (lysophospholipid-acylCoA acyltransferase). Inhibition of this enzyme with organo-mercury compound, like thimerosal, leads to a dramatic increase of LTB4 released by PMNs cells (link).
Leukotriene biosynthesis begins with the specific oxidation of arachidonic acid by a free radical mechanism as a consequence of interaction with 5-LO. A second enzymatic step is also catalysed by 5-LO and involves removal of a hydrogen atom from C-10, resulting in formation of the conjugated triene epoxide LTA4.
The role of leukotrienes in asthma, 2003
TREATMENT OF ASTHMA WITH DRUGS MODIFYING THE LEUKOTRIENE PATHWAY, 1999
Fish or Chips?, 2003
AA percentage of relevant proteins
Receptor for cysteinyl leukotrienes mediating bronchoconstriction of individuals with and without asthma. Stimulation by LTD4 results in the contraction and proliferation of smooth muscle, edema, eosinophil migration and damage to the mucus layer in the lung. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. The rank order of affinities for the leukotrienes is LTD4 >> LTE4 = LTC4 >> LTB4.
Receptor for cysteinyl leukotrienes. The response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. Stimulation by BAY u9773, a partial agonist, induces specific contractions of pulmonary veins and might also have an indirect role in the relaxation of the pulmonary vascular endothelium. The rank order of affinities for the leukotrienes is LTC4 = LTD4 >> LTE4.
Receptor for extracellular ATP > UTP and ADP. The activity of this receptor is mediated by G proteins which activate a phosphatidylinositol-calcium second messenger system. May be the cardiac P2Y receptor involved in the regulation of cardiac muscle contraction through modulation of L-type calcium currents. Is a receptor for leukotriene B4, a potent chemoattractant involved in inflammation and immune response.
Low-affinity receptor for leukotrienes including leukotriene B4. Mediates chemotaxis of granulocytes and macrophages. The response is mediated via G-proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinities for the leukotrienes is LTB4 > 12-epi-LTB4 > LTB5 > LTB3.