LTA4 leukotriene

The carbon sulfur bond in LTC4 is formed by the reaction of glutathione (Section 15 13) with leukotriene A4 (LTA4) LTA4 is an epoxide Sug gest a reasonable structure for LTA4... 

Leukotriene B4, formed by enzymic hydrolysis of LTA4, is chemotactic for macrophages and neutrophils at concentrations as low as 1 ng/ml. The stereochemistry of the conjugated triene subunit was established by synthesis which also made LTB4 available in quantity for biological research. 

LTA4, LXB4, LTC4, LTD4, LTE4 Leukotrienes A4, B4, C4, D4 and Ej Ly-1 (Cell line)... 

FIGURE 26.3 Formation of leukotriene LTA4 by the LOX-5-catalyzed oxidation of arachidonic acid. (From DK MacMillan, E Hill, A Sala, E Sigal, T Shuman, PM Henson, RC Murphy. J Biol Chem 269 26663-26668, 1994. With permission.)... 

The first synthesis of ( )-5,6-epoxy-7,9-( )-ll,14-(Z)-eicosatetraenoate, later identified as the primary leukotriene LTA4 (Ref. 1). 

Figure 6.17. Leukotriene formation in neutrophils. Arachidonic acid, which is released from membrane phospholipids by the action of either phospholipase A2 or diacylglycerol lipase (see Fig. 6.13), is oxygenated by 5-lipoxygenase to yield 5 hydroperoxy-6,8,11,14 eicosa-tetraenoic acid (5-HPETE). This is then converted into 5 hydroxy-6,8,11,14 eicosatetra-enoic acid (5-HETE) and leukotriene (LT) A4. LTA4 may then be enzymically converted into LTC4 and LTB4. LTB4 is the major product in activated neutrophils.

The cytosolic enzyme leukotriene A4 hydrolase (EC 3.3.2.6), which ster-eoselectively converts leukotriene A4 (LTA4) to leukotriene B4 [56], This enzyme catalyzes the hydrolytic cleavage of the 5,6-epoxide ring in LTA4, but, in contrast to what happens with other EHs, the product is not a vicinal diol but a 5,12-diol. As a zinc metalloenzyme, LTA4 hydrolase does not appear to be related to any other epoxide hydrolase. 

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