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Leukotriene biosynthetic enzymes as therapeutic targets
Jesper Z. Haeggström
Jesper Z. Haeggström
Published July 2, 2018
Citation Information: J Clin Invest. 2018;128(7):2680-2690. https://doi.org/10.1172/JCI97945.
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Review Series

Leukotriene biosynthetic enzymes as therapeutic targets

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Abstract

Leukotrienes are powerful immune-regulating lipid mediators with established pathogenic roles in inflammatory allergic diseases of the respiratory tract — in particular, asthma and hay fever. More recent work indicates that these lipids also contribute to low-grade inflammation, a hallmark of cardiovascular, neurodegenerative, and metabolic diseases as well as cancer. Biosynthesis of leukotrienes involves oxidative metabolism of arachidonic acid and proceeds via a set of soluble and membrane enzymes that are primarily expressed by cells of myeloid origin. In activated immune cells, these enzymes assemble at the endoplasmic and perinuclear membrane, constituting a biosynthetic complex. This Review describes recent advances in our understanding of the components of the leukotriene-synthesizing enzyme machinery, emerging opportunities for pharmacological intervention, and the development of new medicines exploiting both antiinflammatory and pro-resolving mechanisms.

Authors

Jesper Z. Haeggström

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Figure 1

Translocation and assembly of the leukotriene biosynthetic complex.

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Translocation and assembly of the leukotriene biosynthetic complex.
Sche...
Schematic model for translocation of cPLA2 and 5-LOX, together with CLP, to the ER and perinuclear membrane, where they meet up with FLAP and LTC4S. LTA4H stays in the cytosolic compartment. Ser phosphorylations of cPLA2 and 5-LOX are indicated. GGT, γ glutamyltransferase; MBD, membrane-bound dipeptidase.
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