2010
DOI: 10.1074/jbc.r110.125880
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Location, Location, Location: Compartmentalization of Early Events in Leukotriene Biosynthesis

Abstract: Over the last 25؉ years, substantial progress has been made in understanding how LTs exert their effects, and a broader appreciation for the numerous biological processes they mediate has emerged. LT biosynthesis is initiated by the action of 5-lipoxygenase (5-LOX), which catalyzes the transformation of AA to LTA 4 in a two-step reaction. Ca 2؉ targets 5-LOX to the nuclear membrane, where it co-localizes with the 5-LOX-activating protein FLAP and, when present, the downstream enzyme LTC 4 synthase, both transm… Show more

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Cited by 49 publications
(33 citation statements)
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“…8,19,21,31,52,67 Along these lines, we note that ATP has a well-established role as an upregulated mediator in inflammation 6870 and that extracellular ATP is measured at elevated levels for patients suffering from inflammatory diseases, such as chronic obstructive pulmonary disease (COPD) and emphysema, which are known to involve leukotrienes as causal factors in their pathology. 7176 Lommatzsch et al recently established that ATP concentrations in bronchoalveolar lavage fluid increased from <10 μM in a control group of patients to >300 μM in patients with increasing stages of COPD.…”
Section: Resultsmentioning
confidence: 94%
“…8,19,21,31,52,67 Along these lines, we note that ATP has a well-established role as an upregulated mediator in inflammation 6870 and that extracellular ATP is measured at elevated levels for patients suffering from inflammatory diseases, such as chronic obstructive pulmonary disease (COPD) and emphysema, which are known to involve leukotrienes as causal factors in their pathology. 7176 Lommatzsch et al recently established that ATP concentrations in bronchoalveolar lavage fluid increased from <10 μM in a control group of patients to >300 μM in patients with increasing stages of COPD.…”
Section: Resultsmentioning
confidence: 94%
“…13 Lipoxygenase structures share a common fold, but the determinants of specificity in the oxidation reaction remain elusive. The current state of understanding is that a helix toward the N-terminus of lipoxygenases (helix 2) contains elements of an entrance to the substrate channel.…”
mentioning
confidence: 99%
“…Certainly chance has dictated some of what we see today. However, it appears that the early steps (involving the most hydrophobic substrates) are catalyzed by membrane bound enzymes (cytochrome P450s in the case of xenobiotic metabolism as well as cyclooxygenases and some lipoxygenases in eicosanoid metabolism)28293031323334. As to the various secondary metabolites, complementary systems with both membrane and soluble enzyme families have evolved.…”
Section: Resultsmentioning
confidence: 99%