Polyunsaturated fatty acid brain

Liu, X., Yamada, N., Maruyama, W., and Osawa, Y. (2008b). Formation of dopamine adducts derived from brain polyunsaturated fatty acids Mechanism for Parkinson s disease.. Biol. Chem. 283,34887-34895. 

Bourre JM, BonneU M, Dumont O, Piciotti M. Nalbone G, Lafont H. High dietary fish oil alters brain polyunsaturated fatty acid composition. Biochim Biophys Acta 1988 960 458 61. 

DIETARY ESSENTIAL FATTY ACIDS, BRAIN POLYUNSATURATED FATTY ACIDS, AND PROSTAGLANDIN BIOSYNTHESIS... 

Brain polyunsaturated fatty acids, either deriving from in situ conversion of linoleic and linolenic acids, or arriving to the brain as preformed compounds, are ultimately found in ester... 

Brain Coordination of the nervous system Glycolysis, amino acid metabolism Glucose, amino acid, ketone bodies (in starvation) Polyunsaturated fatty acids in neonate Lactate ... 

Chan, P.H. and Fishman, R.A. (1980). Transient formation of superoxide radicals in polyunsaturated fatty acid-induced brain swelling. J. Neurochem. 33, 1004-1007. 

Elucidation of the physiological role of arachidonic acid 13 and other polyunsaturated fatty acids, particularly the role of all Z-4,7,10,13,16,19-decosahexaenoic acid 14, found in brain, required the corresponding stable-isotope labelled material1011. The deuteriated phosphonium salt 15, the key intermediate used in the synthesis of title compound 16 (equation 8), has been prepared in 19% overall yield12 starting with ethanol-D6 (equation 7). 

FIGURE 3-7 Pathways for the interconversion of brain fatty acids. Palmitic acid (16 0) is the main end product of brain fatty acid synthesis. It may then be elongated, desaturated, and/or P-oxidized to form different long chain fatty acids. The monoenes (18 1 A7, 18 1 A9, 24 1 A15) are the main unsaturated fatty acids formed de novo by A9 desaturation and chain elongation. As shown, the very long chain fatty acids are a-oxidized to form a-hydroxy and odd numbered fatty acids. The polyunsaturated fatty acids are formed mainly from exogenous dietary fatty acids, such as linoleic (18 2, n-6) and a-linoleic (18 2, n-3) acids by chain elongation and desaturation at A5 and A6, as shown. A A4 desaturase has also been proposed, but its existence has been questioned. Instead, it has been shown that unsaturation at the A4 position is effected by retroconversion i.e. A6 unsaturation in the endoplasmic reticulum, followed by one cycle of P-oxidation (-C2) in peroxisomes [11], This is illustrated in the biosynthesis of DHA (22 6, n-3) above. In severe essential fatty acid deficiency, the abnormal polyenes, such as 20 3, n-9 are also synthesized de novo to substitute for the normal polyunsaturated acids. 

Nitric oxide and peroxynitrite contribute to oxidative damage 569 Production of eicosanoids from polyunsaturated fatty acids such as arachidonic acid may generate reactive oxygen species 570 Brain antioxidant defenses modify ischemia-reperfusion injury 570 Reactive oxygen species may modify both the excitotoxic and the apoptotic components of ischemic brain damage 570... 

The brain has a number of characteristics that make it especially susceptible to free- radical-mediated injury. Brain lipids are highly enriched in polyunsaturated fatty acids and many regions of the brain, for example, the substantia nigra and the striatum, have high concentrations of iron. Both these factors increase the susceptibility of brain cell membranes to lipid peroxidation. Because the brain is critically dependent on aerobic metabolism, mitochondrial respiratory activity is higher than in many other tissues, increasing the risk of free radical Teak from mitochondria conversely, free radical damage to mitochondria in brain may be tolerated relatively poorly because of this dependence on aerobic metabolism. 

Phospholipids in synaptic membranes are an important target in seizures, head injury, neurodegenerative diseases and cerebral ischemia. Synaptic membranes are excitable membranes enriched in phospholipids esterified with the polyunsaturated fatty acids AA and DHA which form a significant proportion of the FFAs rapidly released during ischemia, seizure activity and other brain trauma. 

Free arachidonic acid, along with diacylglycerols and free docosahexaenoic acid, is a product of membrane lipid breakdown at the onset of cerebral ischemia, seizures and other forms of brain trauma. Because polyunsaturated fatty acids are the predominant FFA pool components that accumulate under these conditions, this further supports the notion that fatty acids released from the C2 position of membrane phospholipids are major contributors to the FFA pool, implicating PLA2 activation as the critical step in FFA release [1,2] (Fig. 33-6). 

Bazan, N. G. Supply of n-3 polyunsaturated fatty acids and their significance in the central nervous system. In R. J. Wurtman and J. J. Wurtman (eds), Nutrition and the Brain. New York Raven Press, 1990, pp. 1-24. 

Infants require a substantial supplementation of AA, which is normally supplied through breast milk. Almost 10% of the membrane phospholipid content of breast fed infants was found to be AA in one study (Koletzko et ah, 1996). A crucial factor of the developing infant brain is the amount and type of polyunsaturated fatty acids they receive from their diet. That is, the ratio of dietary n-3 fatty acids (those in which the unsaturation begins 3 carbons from the terminal carbon) to n-6 fatty acids can be optimized to... 

Approximately 60% of the dry weight of the brain is fat, a considerable proportion of which is polyunsaturated fatty acids that are present in plasma membranes. It would not be surprising if replacement of the unsaturated acids by the saturated fatly acids in membrane structure due to a dietary deficiency of polyunsaturated fatty acids played some part in development of mental illness. Indeed, it has been found that supplementation of a normal diet with polyunsaturated fatly acids can improve some mental disorder (see chapter 11). 

Another commercially available product containing naturally occurring marine products is Formulaid , produced by Martek Biosciences as a nutritional supplement for infant formulas. Formulaid contains two fatty acids, arachidonic acid (ARA) and docosahexaenoic acid (DHA), extracted from a variety of marine microalgae. ARA and DHA are the most abundant polyunsaturated fatty acids found in breast milk, and they are the most important fatty acids used in the development of brain gray matter. They are especially desirable for use in infant formulas because they come from nonmeat sources and can be advertised as vegetarian additives to the product. 

Our research group expected that additional polyunsaturated fatty acid ethanolamides may be present in the brain. We also identified in porcine brain another two putative endocannabinoids, namely homo-y-linoleoylethanolamide (K = 53.4 5-5 nM) and 7,10,13,16-docosatetraenoylethanolamide (K = 34.4 3.2 nM). The isolation of these two compounds as constituents of porcine brain that bind to the cannabinoid receptor demonstrated that anandamide is not the sole representative of this class of potential mediators. 

Dietary n-3 polyunsaturated fatty acid depletion activates caspases and decreases NMDA receptors in the brain of a transgenic mouse model of Alzheimer s disease. Eur. J. Neurosci. 22 617-626. 

Kaplan E. and Ansari K. (1984). Reduction of polyunsaturated fatty acid hydroperoxides by human brain glutathione peroxidase. Lipids 19 784-789. 

Kitajka K., Puskas L. G., Zvara A., Hackler L. J., Barcelo-Coblijn G., Yeo Y. K., and Farkas T. (2002). The role of n-3 polyunsaturated fatty acids in brain Modulation of rat brain gene expression by dietary n-3 fatty acids. Proc. Natl. Acad. Sci. USA 99 2619-2624. 

Bourre, J.M., Piciotti, M., Dumont, O., and Durand, G. 1990. Dietary linoleic acid and polyunsaturated fatty acids in rat brain and other organs Minimal requirements of linoleic acid. Lipids 25, 465-472. 

Membrane lipids in brain contain high levels of polyunsaturated fatty acid side chains that are prone to free radical attack. 

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