This is supported by the fact that only one constitutively expressed COX isoform has been identified in the shark Squalus acanthias. In our phylogenetic analysis S. acanthias COX clustered with selleckchem the vertebrate COX 1 clade. Like the putative Daphnia COX pathway, the structure of the daphnid LOX pathway also appeared to be more sim ple than its mammalian counterpart, Inhibitors,Modulators,Libraries which confirms pre vious findings. There was gene sequence evidence that indicated the presence of three leukotrienes in Daph nia LTA4, LTB4 and 12 oxo LTB4. This is, how ever, doubtful since no LTs, nor the precursor 5 HPETE, have been identified in invertebrates and lower verte brates to date. It is possible that the putative LTA4 hydrolase, which is a bi functional enzyme in mammals, having both LTA4 hydrolase and aminopepti dase activity, only has aminopeptidase activity in daph nids as has been reported in Caenorhabditis elegans.

However, recent evidence shows that bi functionality of LTA4H is only six point mutations away in yeast com pared to the mammalian Inhibitors,Modulators,Libraries enzyme. There is reason to believe that daphnid LTA4H may be bi functional, and thus able to convert LTA4 into LTB4. a hypothesis that we will test in future experiments. Furthermore, transcrip tomic evidence from D. magna shows that the expression of leukotriene B4 12 hydroxydehydrogenase increases with increasing concentration of the eicosanoid Inhibitors,Modulators,Libraries inhibiting drug ibuprofen. This does not prove that LTs are present in daphnids, but yet again we cannot rule out the possibility. The enzyme encoded by Ltb4dh is also bi functional in mammals regulating eicosanoids by rapidly degrading different E and F series PGs and LTB4.

The former Inhibitors,Modulators,Libraries function of LTB4DH appears to be the most likely in daphnids until solid proof exits about the presence of LTs. The presence of lipoxins is, however, more likely, and Inhibitors,Modulators,Libraries bio informatic information from D. pulex suggests that at least two LOX enzymes are present. LOX enzymes have been found in all organisms studied, from bacteria to man. The two putative D. pulex LOXs are both composed by two domains. an N terminal lipase domain belonging to the InterPro protein family 734 and a C terminal LOX LH2 domain. This resembles mammalian LOX enzymes that are also comprised of two domains. a regulatory N terminal domain that is similar to mammalian lipases and a catalytic LOX domain.

LOX LH2 is the only LOX related domain that has been identified in the D. pulex genome. Other known LOX domains include e. g. mammalian LOX and LOX, C terminal. There are 13 D. pulex gene models that contain the LOX LH2 domain, but only two genes contain both an N ter minal domain similar selleck kinase inhibitor to mammalian lipases and a C terminal LOX domain. Further investigations are needed to specify what type of LOX enzyme these two Daphnia sequences represent prior to analysing their phylogenetic relationship.