HUFA

In experimental assay systems, free fatty acids (FFAs) destroy red blood cells and show hemolytic activity (39). Free fatty acids, especially the highly unsaturated fatty acids (HUFAs) contained in the raphidophyte flagellates, have been implicated as one of the causative substances that damage the epithelial tissues of the fish gills. 

The essential dietary fatty acids include linolenic acid (LA, C18 2 co6) and alpha-linolenic acid (LN, C18 3 oo3). Mammals are missing a fatty acid desaturase capable of introducing a double bond between C9 and the methylene end of the fatty acid. Hence, to synthesize essential HUFAs, LA and LN are both required in the diet (Fig. lb). LA is the precursor to arachi-donic acid (AA, C20 4 006) and derivative eicosanoids, whereas LN is the precursor to eicosapentaenoic acid (EPA, C20 5 oo3), docosahexaenoic acid (DHA,C22 6 oo3), and oo3-derived... 

The HUFAs (AA, EPA, and DHA), required by mammals, are synthesized by the microsomal elongases and A5 and A6 desaturases (8). The substrates for synthesis, LA and LN, are obtained primarily from vegetable oils in the diet. Elongation and desaturation of LA produces AA, whereas elongation and desaturation of LN produces EPA and DHA. Synthesis of DHA, which is concentrated in the brain, proceeds through the elongation and desaturation pathways to the product C24 6 (1)3, which is then the substrate for one cycle of peroxisomal fS-oxidation to yield C22 6 (u3 (8). 

Fats are best fed back to the same species. Tallows are best used by cattle. Fish oils should only be used in levels that do not cause off-flavors in eggs, broilers, pork, or bacon. They are not recommended for cats and mink because of potential steatitis problems (67), unless the diet is adequately supplemented with vitamin E. Fish oils are valuable in growing fish, and are more effective in feeds if obtained from species whose metabolism focuses on the same HUFA family (n-6 or n-9) as the species cultivated. 

Furthermore, a diet with low contents of FA may be involved in the development of insulin resistance, which suggests that an appropriate dietary intake of n-3 PUFA is considered protective against metabolic syndrome [183]. In addition, diverse psyquiatric impairs (depression, bipolar disorders, schizophrenia, autism) and neurodegenerative diseases such as Alzheimer disease have been associated to decreased blood levels of n-3 HUFA. Besides, there are many examples about the use of pol)nmsaturated FA as drugs. Thus, EPA has shown efficacy as adjunctive treatment, and in some cases as the only treatment in several psyquiatric disorders [184]. It is suggested that the potential of n-3 FA to prevent recurrence and metastasis of mammary cancer when used in adjuvant therapy is associated with a n-6 to n-3 ratio lower than 2 1 [185], On the other hand, fish intake is considered as a protective factor for preventing prostate cancer in addition, in humans low levels of ALA in mammary adipose tissue are associated with an increased risk of breast cancer in women [186]. 

The phospholipase A2 (PLAi) series of enzymes remove fatty acids, usually highly unsaturated fatty acids (HUFAs) from the Sn2 position of phospholipids, creating a free HUFA and a lysophospholipid (LyPL), a phospholipid without a fatty acid at the Sn2 position (Fig. 1). There are many PLA2 enzymes, but in the brain the most important ones are the calcium-dependent and calcium-independent cytosolic PLA2S (cPL A2S) (Horrobin... 

Lysophospholipids and HUFAs are highly active cell signalling molecules with many different actions... 

The brain is unusual in being extremely rich in HUFAs at the Sn2 position. These HUFAs come from two classes of fatty acids the so-called omega-3 and omega-6 essential fatty acids (Fig. 3). These are called essential because at least one of each series, usually linoleic of the omega-6 and a-linolenic of the omega-3 series, must be provided... 

There is now substantial evidence from several groups that, although plasma levels of AA and other HUFAs are normal or near normal, red cell membrane phospholipid levels are reduced, particularly in patients with the negative syndrome (Peet, Laugharne, Horrobin, Reynolds, 1994 Yao, van Kammen, Welker, 1994 Glen etal., 1994). The abnormality may become more evident if red cells are not frozen immediately at very low temperatures, such as -70°C. Maintenance for a period at room temperature or for long periods at -20°C rather than -70°C is associated with loss of AA from membrane phospholipids in samples from schizophrenic patients but not from controls. This indicates increased loss of AA from membranes, a process that may continue in stored samples. 

N.-H. Norsker, G. Stottrup (1994). The importance of dietary HUFAs for fecundity and HUFA content in the harpacticoid, Tisbe holothuriae Humes. Aquaculture, 125, 155-166. 

Abbreviations a-BFAs anteiso-branched fatty acids AGP acyl carrier protein BHLH active soluble domain of SREBP CNS central nervous system DSD delta 5 desaturase D6D delta 6 desaturase ER endoplasmic reticulum Hik histidine kinase HUFA highly unsaturated fatty acid LXR liver X receptor MUFA monounsaturated fatty add NF-Y nuclear factor Y PLs phospholipids PP peroxisome proliferator PPAR PP-activated receptor PPRE PP response element PUFA polyunsaturated fatty acid PUFA-BP PUFA binding protein PUFA-RE PUFA response element RXR retinoid X receptor SCAP SREBP cleavage-activating protein SCD steraroyl CoA desaturase SFA saturated fatty acid SRE sterol response... 

Elovl-2 (formerly denoted as Ssc2) is involved in the biosynthesis of the n - 3 and n - 6 series of highly unsaturated fatty acids (HUFA). Expression studies in yeast demonstrated that Elovl-2 is able to efficiently elongate 20- and 22-carbon PUFA but is unable to elongate 18-carbon SFA, MUFA, and PUFA. Elovl-2 is predominantly expressed in the testis, a tissue in which HUFA are synthesized in high levels (A. Leonard, 2(X)2). 

DHA plays a major part in learning spatial tasks and olfactory-based learning and has been reported to improve symptoms of human patients with dementia including Alzheimer s disease. DHA improves neuronal cell survival and differentiation and is involved in neurotransmitter recycling. By slowing the ion channel activity, n - 3 HUFA may also alleviate the symptoms of convulsive seizures, which are characterized by uncontrolled firings of neurons in the central nervous system. 

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