Arachidonic acid cyclooxygenase reaction products

Classically, inflammation is a protective reaction of the body in response to some physical, chemical, or microbial injury and insult of the cells. Acute inflammation, rapid onset and shorter duration, is considered as a healthy response. However, when inflammation continues for prolonged period of time, it becomes detrimental and may raise the first step of a chronic disease (Medzhitov, 2008). Arachidonic acid/COX and nuclear factor- (NF- ) are well known inflammatory pathways which induce production of inflammatory mediators such as prostaglandins, thromboxanes, leukotrienes, and cytokines. Most commonly accepted mechanism of anti-inflammation is inhibition of cyclooxygenase (COX) activity. There are two kinds of cyclooxygenases COX-1 is natural protective enzyme of intestinal mucosa while COX-2 is induced by tissue damage as an inflammatory mediator (Maroon et al., 2006). NF- is a recently identified... 

Monoamine oxidase, tyrosine hydroxylase, and L-amino acid oxidase generate hydrogen peroxide as their reaction product. Hydrogen peroxide is also produced by auto-oxidation of catecholamines in the presence of vitamin C. Moreover, phospholipase A2 (PLA2), cyclooxygenase (COX), and lipoxygenase (LOX), the enzymes associated with arachidonic acid release and the arachidonic acid cascade,... 

The peroxidase reaction (Figure 12.7a) can function in the absence of cyclooxygenase activity, because the intermediate product (prostaglandin G2) can be provided by another enzyme molecule. In accord with this model, a sample of cyclooxygenase, when expressed recombinantly and in the absence of arachidonic acid substrate, will initially be inactive, but it will exhibit burst kinetics upon first contact with arachidonic acid, due to the cascading activation of more and more enzyme molecules by PGG2". ... 

Inflammation is a normal and complex reaction by the body to an injury. Aloe has been used in traditional medicine for its anti-inflaimnatoiy use. The aqueous and chloroform extracts of aloe inhibit the effect on carrageen induced edema. This effect was associated with an inhibitory action on the arachidonic acid pathway via cyclooxygenase 68). Aloe gel components were able to suppress bacterial induced pro-inflarmnatoiy production of cytokines (systematically elevated after a bacterial invasion), namely TNF-a and IL-p 69). 

The finding that the endoperoxides caused platelet aggregation made it of interest to study the transformations of arachidonic acid in suspensions of human platelets. Two pathways were identified [16]. The initial reaction of one of them was catalyzed by fatty acid cyclooxygenase and led to the formation of three major end-products, i.e. 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT), malondialdehyde, and a novel hemiacetal derivative named thromboxane 82 (TXBj). The other pathway consisted of conversion of arachidonic acid into 12L-hydroperoxy-5,8,10,14-eicosatetraenoic acid (12-HPETE) by a novel lipoxygenase. The hydroperoxide was subsequently converted into a stable end-product, 12L-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) by a glutathione peroxidase [16,17]. 

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