Arachidonic acid transport

Transport in the blood is no longer a requisite for a hormonal response. Responses can occur after release of hormones into the interstitial fluid with binding to receptors in nearby ceUs, called paracrine control, or binding to receptors on the ceU that released the hormone, called autocrine control. A class of hormones shown to be synthesized by the tissue in which they act or to act in the local ceUular environment are the prostaglandins (qv). These ubiquitous compounds are derived from arachidonic acid [506-32-1] which is stored in the ceU membranes as part of phosphoHpids. Prostaglandins bind to specific ceUular receptors and act as important modulators of ceU activity in many tissues. 

Figure 6 Anandamide metabolism NAPE, N-arachidonylphosphatidyl-ethanol-amides PLD, phospholipase D AEA, anandamide AC, anandamide carrier protein AT, anandamide transporter AEAase, anandamide amidase AA, arachidonic acid.

Mitochondria, nitric oxide synthase and arachidonic acid metabolism are sources of reactive oxygen species during ischemia-reperfusion injury. ROS generation during ischemia-reperfusion may come from several sources, including NOS activity, mitochondrial electron transport, multiple steps in the metabolism of arachidonic... 

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. 

Ingram, S. L. and Amara, S. G. (2000) Arachidonic acid stimulates a novel cocaine-sensitive cation conductance associated with the human dopamine transporter. J. Neurosci. 20,550-557. 

Zerangue, N Arriza, J. L., Amara, S. G., and Kavanaugh, M. P. (1995) Differential modulation of human glutamate transporter subtypes by arachidonic acid. J. Biol. Chem. 270, 6433-6435. 

Trotti, D., Volterra, A., Lehre, K. P., Rossi, D., Gjesdal, O., Racagni, G and Danbolt, N. C. (1995) Arachidonic acid inhibits a purified and reconstituted glutamate transporter directly from the water phase, and not via the phospholipid membrane. J. Biol. Chem. 270, 9890-9895. 

Fairman, W. A., Sonders, M. S., Murdoch, G. H and Amara, S. G. (1998) Arachidonic acid elicits a substrate-gated proton current associated with the glutamate transporter EAAT4. Nat. Neurosci. 1,105-113. 

Fig. 4.4 Hypothetical model showing the modulation of glutamate transporter by arachidonic acid. Interactions of glutamate with its receptor result in depolarization and Ca2+ entry into the cell. Ca2+-mediated stimulation of PLA2 results in breakdown of neural membrane phospholipids and the release of arachidonic acid. Arachidonic acid not only modulates proton conductance associated with neuronal excitability, but also provides eicosanoids, which may control the glutamate transporter (modified from Fairman and Amara, 1999)...

Chow, S.L., and D. Hollander. 1978. Arachidonic acid intestinal absorption Mechanism of transport and influence of luminal factors of absorption in vitro. Lipids 13 768. 

It has been suggested that an increased production of arachidonic acid following down-regulation of annexin 1 in CF patients may explain some of the associated complications of the disease (Carlstedt-Duke et al., 1986 Strandvik et al., 1988). This is based on the observation that lymphocytes from CF patients show defective inhibition of AA production by dexamethasone. Increased AA production has been reported in CF and would influence chloride transport, mucus production and calcium homeostasis (and production of the eicosanoids). The reason why annexin 1 expression is reduced in these patients is at present unclear. 

Arachidonic acid (5,8,11,14-eicosatetraenoic acid), a polyunsaturated fatty acid derived from dietary sources or by desaturation and chain elongation of the essential fatty acid linoleic acid, is found widely in the body. It is transported in a protein-bound state and stored in the phospholipids of cell membranes in all tissues of the body [108] from where it can be changed into biologically... 

Anandamide can be transported inside neural cells (neurons and glia) by a carrier-mediated facilitate diffusion mechanism (Beltramo et al., 1997) and transformed through two main pathways (1) hydrolysis to arachidonic acid and ethanolamine, and (2) oxidation to various oxygenated derivatives. 

AG is internalized inside the cells through either passive diffusion or carrier-mediated transport. Once inside the cell, 2-AG can be transformed through three main mechanisms (1) hydrolysis to arachidonic acid and glycerol (2) oxidation to a series of oxygenated derivatives and (3) anabolic metabolism (Fig. 2). 

Fig. 1. A model for the pleiotropic effects of LH on functions of Leydig cells. LH interacts with its specific receptor in the plasma membrane of the Leydig cell which results in the activation of several transducing systems and the formation of several second messengers (cyclic AMP, Ca2+, diacylglycerol and arachidonic acid metabolites). Protein kinases (A, C and calmodulin dependent) are activated resulting in the phosphorylation of specific proteins and the synthesis of specific proteins. The (phospho)proteins are involved in the transport of cholesterol to, and the control of, cholesterol metabolism in the inner mitochondrial membrane. Arachidonic acid metabolites (prostaglandins, leukotrienes) may also control steroidogenesis. LH can also regulate the secretion of proteins. The trophic effects of LH are manifested in the growth and differentiation of the Leydig cells.

Fig. 2.8. Factors controlling the production of free radicals in cells and tissues (Rice-Gvans, 1990a). Free radicals may be generated in cells and tissues through increased radical input mediated by the disruption of internal processes or by external influences, or as a consequence of decreased protective capacity. Increased radical input may arise through excessive leukocyte activation, disrupted mitochondrial electron transport or altered arachidonic acid metabolism. Delocalization or redistribution of transition metal ion complexes may also induce oxidative stress, for example, microbleeding in the brain, in the eye, in the rheumatoid joint. In addition, reduced activities or levels of protectant enzymes, destruction or suppressed production of nucleotide coenzymes, reduced levels of antioxidants, abnormal glutathione metabolism, or leakage of antioxidants through damaged membranes, can all contribute to oxidative stress.

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