Arachidonic acid biochemical pathway

Zeldin DC, Moomaw CR, Jesse N, Tomer KB, Beetham J, et al. 1996. Biochemical characterization of the human liver cytochrome P450 arachidonic acid epoxygenase pathway. Arch Biochem Biophys 330 87-96. 

By interfering with any one of the many phases associated with these second messenger pathways, toxins may alter channel gating. For example, the blue green algal toxins, aplysiatoxin, and lyngbyatoxin bind to and activate protein kinase C in a manner similar to phorbol esters (73). They also stimulate arachidonic acid metabolism (74). The coral toxin, palytoxin, also stimulates arachidonic acid breakdown albeit by an unknown mechanism (74) and affects other biochemical activities of the cell (see chapters by Fujiki et al., Wattenberg et al., and Levine et al., this volume). 

Some polyphenols inhibit platelet aggregation reducing the risk of thrombosis [171-173]. This effect may be due to a series of interaction of flavonoids in different biochemical pathways, such as by inhibition of cyclooxygenase and lipoxygenase, that are involved in the arachidonic acid metabolism in the platelets, or by inhibition of the formation of tromboxane and of the receptor function of the same [173-176]. Regular consumption of wine, tea and chocolate has been associated to the reduction of platelet aggregation, cardio-vascular diseases and thrombosis [171,177-179]. 

The benzodioxole ring system is distributed widely in nature and is found in numerous natural products such as safrole and piperonal, as well as a multitude of alkaloids. 1,2-Dioxolanes are intermediates in the arachidonic acid cascade, which is the biochemical pathway from essential fatty acids to prostaglandins and similar hormones. The endoperoxide PGH2 (121) is believed to be formed on initial oxidation of arachidonic acid (120). PGH2 has a half-life of 4-5 minutes and is transformed enzymatically into prostaglandins, prostacyclin and the thromboxanes. These compounds are mediators for the control of platelet aggregation, blood vessel dilation and smooth muscle contraction. 

Mahadevappa VG, and Holub BJ. (1986). Diglyceride pathway is a minor source o( released arachidonic acid in thrombin-stimulated platelets. Biochem. Biophys. Res. Commun. 134,1327-1333. 

Maccarrone M, Salvati S, Bari M, Finazzi-Agro A (2000b) Anandamide and 2-arachidonoyl-glycerol inhibit fatty acid amide hydrolase by activating the lipoxygenase pathway of the arachidonate cascade. Biochem Biophys Res Commun 278 576-583... 

Mahadevappa VG, Holub BJ. Diacylglycerol lipase pathway is a minor source of released arachidonic acid in thrombin-stimulated human platelets. Biochem Biophys Res Commun 1986 134 1327-1333. Maiese K, Holloway HH, Larson DM. Soncrant TT. Effect of acute and chronic arecoline treatment on... 

Fig. 6. Biochemical pathway of the metabolism of arachidonic acid into the biologically active leukotrienes. Arachidonic acid released from phospholipids by cytosolic (c) phospholipase Aja is metabolized by 5-lipoxygenase to 5-hydroperoxyeicosatetraenoic acid (5-HpETE) and leukotriene A4 (LTA4) which is then enzymatically converted into leukotriene B4 (LTB4) or conjugated by glutathione to yield leukotriene C4 (LTC4).

AbuBakar S, Boldogh I, Albrecht T. Human cytomegalovirus stimulates arachidonic acid metabolism through pathways that are affected by inhibitors of phospholipase A2 and protein kinase C. Biochem Biophys Res Commun 1990 l66(2) 953-9. 

The defense mechanisms of G. vermiculophylla seem to involve the arachidonic acid pathway that can lead to prostaglandins and hydroxylated unsaturated fatty acid, such as members of the HETE family. Addition of H-labeled arachidonic add to wounded alga showed that labeled fatty acids were generated rapidly. Interestingly, these results suggested that the enzymatic processes necessary for the activation of the defense mechanism remained viable, despite the damage to the tissues. The metabolomic assay used validated the existence of the chanical defenses and characterized the mechanisms and biochemical pathways involved. 

An initial series of studies provided evidence that SRS-A was likely to be an arachidonic acid metabolite produced by a biochemical pathway distinct from cyclooxygenase. This evidence was based on chemically impure preparations of SRS-A, however, and so remained circumstantial until 1979, when the coupling of a relatively new analytical technique (high-performance liquid chromatography, HPLC) with classical bioassay methods allowed Robert C. Murphy, Bengt Samuelsson and their collaborators at the... 

Over the past three decades, the metabolic pathways responsible for the storage, mobilization and metabolism of arachidonic acid in animal tissues have been studied in great detail. Many of the enzymes involved in these biochemical reactions have been characterized, and drugs that interfere with them have been described. Thousands of publications have documented the pharmacological actions exerted by arachidonic acid and its metabolites, collectively known as the eicosanoids, on all systems and organs of the body, as well as their possible physiological roles. 

It is now possible to inhibit the metabolism of arachidonic acid at many sites in the biochemical pathways. Some of the agents are too toxic for use in vivo. 

Discussion of the nutritional requirement for unsaturated fatty acids and recent biochemical work on pathways from arachidonate to prostaglandins advanced level. 

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