Metabolism of, arachidonic acid

CYP2J2 is abundant in cardiovascular tissue and active in the metabolism of arachidonic acid to eicosanoids that possess potent anti-inflammatory, vaso-dilatory, and fibrinolytic properties. Polymorphic alleles with reduced function are known. Some other CYP2 subfamilies and isozymes listed in Table 1 are still not well characterized, in part because most of them were discovered in the course of the human genome project. 

Prostaglandin Any of a large group of biologically active, carbon-20, unsaturated fatty acids that are produced by the metabolism of arachidonic acid through the cyclooxygenase pathway. 

Detailed studies on the metabolism of arachidonic acid (AA) in the nervous system of the opisthobranch mollusc Aplysia califomica were carried out [21]. A. califomica provides a very useful model for neurobiological studies since its... 

Scheme 5. Proposed biosynthesis of allene oxide 64 from 8i -lipoxygenase initiated metabolism of arachidonic acid and subsequent non-enzymatic transformations to racemic cyclopenteone 30 [86]...

FIGURE 32-7 Sources of free radical formation which may contribute to injury during ischemia-reperfusion. Nitric oxide synthase, the mitochondrial electron-transport chain and metabolism of arachidonic acid are among the likely contributors. CaM, calcium/calmodulin FAD, flavin adenine dinucleotide FMN, flavin mononucleotide HtT, tetrahydrobiopterin HETES, hydroxyeicosatetraenoic acids L, lipid alkoxyl radical LOO, lipid peroxyl radical NO, nitric oxide 0 "2, superoxide radical. 

Powell PK, Wolf I, Jin R, et al. Metabolism of arachidonic acid to 20-hydroxy-5,8,11, 14-eicosatetraenoic acid by P450 enzymes in human liver involvement of CYP4F2 and CYP4A11. J Pharmacol Exp Ther 1998 285(3) 1327-1336. 

The acid-soluble SH-groups in platelets are mainly those of glutathione (GSH). GSH is a cofactor for enzymes such as peroxidase. If feverfew is able to interfere with this cofactor, enzyme function may be impaired. One pathway that may be affected in this way is the metabolism of arachidonic acid (Figure 6.1). In the presence of feverfew extract an increase was found in lipoxygenase product formation and impaired conversion of HPETE to HETE, for which GSH is a cofactor [52]. Inhibition of the liberation of [ " C]arachidonic acid from phospholipids was also found [53], which implies impairment of phospholipase A2 activity and for which SH-groups are thought to be important. 

Diethylcarbamazine citrate (Hetrazan) is active against several microfilaria and adult filarial worms. It interferes with the metabolism of arachidonic acid and blocks the production of prostaglandins, resulting in capillary vasoconstriction and impairment of the passage of the microfilaria. Diethylcarbamazine also increases the adherence of microfilariae to the vascular wall, platelets, and granulocytes. 

The actions of non-steroidal anti-inflammatory drugs appear to be diverse. Phenylbutazone and sulfmpyrzone inhibited several effects of FMLP on PMNs increased adhesiveness, stimulation of the hexosemonophosphate shunt, lysosomal enzyme release, and formation of O These effects were explained by the ability of both phenylbutazone and sulfinpyrazone to inhibit binding of labelled FMLP to PMNs. Both were selective in that neither inhibited responses of PMNs to Csa and neither inhibited the stimulation of the hexose monophosphate shunt by latex or by opsonized Candida. The responses of PMNs to FMLP, including the release of O have also been inhibited by 5,8,11,14 eicosatetraynoic acid, an inhibitor of the metabolism of arachidonic acid h by indomethacin and by... 

Kerkhoff C, Klempt M, Kaever V, Sorg C. 1999. The two calcium-binding proteins, S100A8 and S100A9, are involved in the metabolism of arachidonic acid in human neutrophils. J Biol Chem 274(46) 32672-32679. 

Thromboxane A2 (TxA2) is an exceptionally potent pro-aggregatory and vasoconstrictor substance produced by the metabolism of arachidonic acid in blood... 

COX-2 are mainly involved in PGI2 formation and in the inflammatory process. COX-2 is inducible, for example, by pro-inflammatory cytokines and growth factors, implying a role for COX-2 in both inflammation and the control of cell growth. It promotes early atherosclerotic lesion formation in LDL receptor-deficient mice in vivo, and COX-2 is the enzyme responsible for most of the metabolism of arachidonic acid in the macrophage. 

FIGURE 26.3 Metabolism of arachidonic acid and eicosapentaenoic acid via the cyclooxygenase and lipoxygenase pathways. 

Corvazier, E. and Maclouf, J. 1985. Interference of some flavonoids and non-steroidal antiinflammatory drugs with oxidative metabolism of arachidonic acid by human platelets and neutrophils. Biochem. Biophys. Acta 835, 315-321. 

Another important metabolic pathway for the metabolism of arachidonic acid the 5-lipooxygenase pathway, which leads to a series of compounds callea leukotrienes (LTs). These compounds appear to be essentially, but not exclusively, of a pathophysiologic nature and are formed in various inflammatory cells. 

Figure 9.5. CYP epoxygenase- and hydroxylase-mediated metabolism of arachidonic acid. Products include biologically active EETs and HETEs. (Adapted from Seubert et al. Prostaglandins and Other Lipid Mediators 82, 50-59, 2007.)...

Luo, M., Flamand, N., and Brock, T.G., Metabolism of arachidonic acid to eicosanoids within the nucleus, Biochim. Biophys. Acta 1761, 618-625, 2006 Balboa, M.A. and Balsinde, J., Oxidative stress and arachidonic acid mobilization, Biochim. Biophys. Acta 1761, 385-391, 2006. 

Chen JK, Capdevila J, Harris RC. Cytochrome p450 epoxygenase 118. metabolism of arachidonic acid inhibits apoptosis. Mol. Cell Biol. 2001 21 6322-6331. 

In order to study the metabolism of arachidonic acid by the cytochrome P450 complex, Nithipatikom et al. [38] developed a negative-ion LC-ESI-MS method for the quantitative determination of 5,6-, 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acids (EET), their corresponding diHET, and 20-HETE. The analytes and their deuterium-labelled internal standards were measured as [M-H] in selected-ion monitoring (SIM) mode. The detection limit was 1 pg (2-mm-ID column). 

W. S. Powell and D. F. Cohn, Metabolism of arachidonic acid and other polyunsaturated fatty acids by blood vessels, Prog. Lipid Res. 26 183-210 (1987). 

All NSAIDs, by definition, inhibit COX enzymes to some degree. This prevents the metabolism of arachidonic acid to the unstable endoperoxide intermediate PGG2 (Ziel Krupp 1975). Currently two isoforms of the COX enzyme, known as COXl and COX2, have been described (Vane Dotting... 

Which of the following statements concerning metabolism of arachidonic acid is TRUE ... 

Srivastava KC. Effects of aqueous extracts of onion, garlic, and ginger on platelet aggregation and metabolism of arachidonic acid in the blood vascular system in vitro study. Prostagland Leukotr Med 1984 13 227-235. 

---