Editing Lipoxin (section)

===Synthesis===
Formation of LXs is conserved across a broad range of animal species from fish to humans.<ref name="pmid16046112">{{cite journal | vauthors = Levy BD | title = Lipoxins and lipoxin analogs in asthma | journal = Prostaglandins, Leukotrienes, and Essential Fatty Acids | volume = 73 | issue = 3–4 | pages = 231–7 | year = 2005 | pmid = 16046112 | doi = 10.1016/j.plefa.2005.05.010 }}</ref>  Biosynthesis of the LXs requires two separate enzymatic attacks on arachidonic acid (AA). One attack involves attachment of a hydroperoxy  (-O-OH) residue to carbon 15, conversion of this species to a 14,15-[[epoxide]], and the resolution of this epoxide to form either 14,15-dihydroxy-eicosatetraenoate or 15-hydroxy-eicosatetraenoate products. This step is catalyzed by enzymes with [[15-lipoxygenase]] activity, which in humans includes [[ALOX15]], [[ALOX12]], aspirin-treated [[cyclooxygenase 2]], and [[cytochrome P450]]s of the microsomal, mitochondrial, or bacterial subclasses. [[ALOX15B]] may also conduct this metabolism. The other enzyme attack point forms a 5,6-[[epoxide]] which is resolved to either 5,6-dihydroxy-eicosatetraenoate or 5-hydroxy eicosatetraenoate products; this step catalyzed by [[5-lipoxygenase]] (ALOX5). Accordingly, these double oxygenations yield either 5,6,15-trihydroxy- or 5,14,15-trihydroxy-eicosatetraenoates.<ref name="pmid25895638">{{cite journal | vauthors = Romano M, Cianci E, Simiele F, Recchiuti A | title = Lipoxins and aspirin-triggered lipoxins in resolution of inflammation | journal = European Journal of Pharmacology | volume = 760 | pages = 49–63 | year = 2015 | pmid = 25895638 | doi = 10.1016/j.ejphar.2015.03.083 }}</ref><ref name="pmid26853678">{{cite journal | vauthors = Markworth JF, Maddipati KR, Cameron-Smith D | title = Emerging roles of pro-resolving lipid mediators in immunological and adaptive responses to exercise-induced muscle injury | journal = Exercise Immunology Review | volume = 22 | pages = 110–34 | year = 2016 | pmid = 26853678 }}</ref> The double oxygenations may be conducted within a single cell type which possesses ALOX5 and an enzyme with 15-lipoxygenase activity or, alternatively, by two different cell types, each of which possesses one of these enzyme activities. In the latter '''transcellular biosynthetic pathway''', one cell type forms either the 5,6-dihydroxy-, 5-hydroxy-, 14,15-dihydroxy- or a 15-hydroxy-eicosatetraenoate, and then passes this intermediate to a second cell type, which metabolizes it to the final LX product.<ref name="pmid26457057">{{cite journal | vauthors = Chandrasekharan JA, Sharma-Walia N | title = Lipoxins: nature's way to resolve inflammation | journal = Journal of Inflammation Research | volume = 8 | pages = 181–92 | year = 2015 | pmid = 26457057 | pmc = 4598198 | doi = 10.2147/JIR.S90380 | doi-access = free }}</ref> For example, LXs are formed by platelets which, lacking ALOX5, cannot synthesize them. Rather, [[neutrophils]] form the 5,6-epoxide [[Leukotriene A4|leukotriene A<sub>4</sub>]] (LTA<sub>4</sub>) via ALOX5, and pass it to platelets that then reduce it to a 5,6-dihydroxy-eicosateteraenoate product and further metabolize it through ALOX12 to form the 15-hydroxy product, LXA<sub>4</sub>.<ref name="pmid25895638"/> The two LXs are distinguished from their 15-epi-LTX epimers by their structural formulae:

*LxA<sub>4</sub>: 5''S'',6''R'',15''S''-trihydroxy-7''E'',9''E'',11''Z'',13''E''-eicosatetraenoic acid
*LxB<sub>4</sub>: 5''S'',14''R'',15''S''-trihydroxy-6''E'',8''Z'',10''E'',12''E''-eicosatetraenoic acid
*15-epi-LxA<sub>4</sub>: 5''S'',6''R'',15''R''-trihydroxy-7''E'',9''E'',11''Z'',13''E''-eicosatetraenoic acid    
*15-epi-LxB<sub>4</sub>: 5''S'',14''R'',15''R''-trihydroxy-6''E'',8''Z'',10''E'',12''E''-eicosatetraenoic acid
 
Note that the two LXs have their 15-hydroxyl residues in the ''S'' [[chirality]] configuration because all of the ALOX enzymes form 15''S''-hydroxy AA products. In contrast, the 15-hydroxy residues of the two epi-LXs are 15''R'' chirality products because they are synthesized by aspirin-treated cyclooxygenase 2 or the microsomal, mitochondrial, or bacterial [[cytochrome P450]]s; these enzymes form almost entirely or partly 15''R''-hydroxy products.<ref name="pmid25895638"/> (15-Epi-LxA<sub>4</sub> and 15-epi-LxB<sub>4</sub> are sometimes termed AT-LxA<sub>4</sub> and AT-LxB<sub>4</sub>, respectively, when acknowledging their formation by aspirin-treated cyclooxygenase 2, i.e. by '''A'''spirin-'''T'''riggered cyclooxygenase 2.)

In addition to the pathways cited above, other transcellular metabolic routes have been shown to make LXs. For example, [[5-lipoxygenase]] (i.e. ALOX5) in neutrophils and [[15-lipoxygenase]]-1 (i.e. ALOX15) in immature erythrocytes and reticulocytes operate in series to form LxA<sub>4</sub> and LxB<sub>4</sub>; this pathway also occurs in serial interactions between neutrophils and eosinophils; between [[epithelium]] or [[Macrophage#Subtypes|M2 macrophage]]s/monocytes and neutrophils; and [[endothelium]] or skeletal muscle and neutrophils.<ref name="pmid25895638"/><ref name="pmid26853678"/><ref name="pmid26457057"/>