: Overview of EFA metabolism

Transcription

1 Figure 1 gives an overview of the metabolic fate of the EFAs when consumed in the diet. The n-6 and n-3 PUFAs when consumed in the form of dietary triglyceride from various food sources undergoes digestion in the small intestine which allows for absorption, transport in the blood, and subsequent assimilation within tissues themselves through the body (including brain, retina, heart, and other tissues). As depicted in Figure 1, the EFAs can undergo cellular beta oxidation to provide cellular energy in the form of ATP as for the more common and prevalent saturated, monounsaturated fatty acids (MUFAs) and any trans fatty acids that might be present in the diet. EFAs can also undergo esterification into cellular lipids including triglyceride, cholesterol ester, and phospholipid. The essential fatty acids which are assimilated into triglyceride forms are often stored therein until required later for subsequent metabolism and functioning. As such, the EFAs will be released from the stored triglyceride forms by enzymatic/hydrolytic processes. EFAs can also be temporarily stored as esterified fatty acids to a cholesterol backbone (as cholesterol ester); the EFAs can subsequently be released from the cholesterol ester forms and utilized for subsequent metabolism as well. The EFAs which are assimilated into phospholipid are particularly important in the overall structure-function of both omega-6 and omega-3 fatty acids since these membrane forms (as phospholipids) maintain both the structural integrity and the critical functioning of cellular membranes throughout the body. Finally, and very importantly, the dietary EFAs present as linoleic acid (LA) and as alpha-linolenic acid (ALA) are activated to high-energy forms known as fatty-acyl CoA which provides for the conversion of these dietary PUFAs into their important longer-chain and more polyunsaturated products as derived by a series of desaturation plus elongation reactions which are particularly active in the liver and to a lesser extent in other tissues. Figure 1 : Overview of EFA metabolism 1 / 8

2 From the above discussions, it is apparent that some of the fatty acids which appear in the cells and tissues within the human body are derived directly from dietary sources and/or by way of endogenous synthesis within the body itself. The sources of the major physiologically-occurring fatty acids in the human body are outlined in Table 1 Table 1: Sources of major physiologically-occurring fatty acids (in human body) Physiological Fatty Acid(s) Dietary Source Endogenous (in-body) synthesis A) Saturates 16:0 (de-novo) 2 / 8

3 18:0 (elongation from 16:0) B) Monounsaturates (MUFAs) cis - 18:1 n-9 (desaturation of 18:0) Trans - 18:1 3 / 8

4 No C) Polyunsaturates (PUFAs) 18:2n-6, LA No 18:3n-3, ALA No 4 / 8

5 20:4n-6, AA * 20:5n-3, EPA ** 22:6n-3, DHA ** *Requires metabolic precursor (LA) to be present ** Requires metabolic precursor ( ALA ) to be present (limited conversion from ALA to EPA + DHA) As seen in the Table 1, the saturated fatty acids (e.g., 18:0, a saturated fatty acid of 18 carbons in chain length with no double bonds) can be readily synthesized in the body from the 5 / 8

6 two carbon unit known as acetate (acetyl-coa in its active cellular form). In addition, saturated fatty acids are derived from dietary sources and can be metabolized by desaturation reactions (insertion of a double bond enzymatically) to convert it into a monounsaturated fatty acid (18:1 with one double bond in the molecule which is designated as an n-9 since the double bond is adjacent to the 9 th carbon counting from the methyl end). It is noteworthy in Table 1 that LA and ALA in the body can only be derived by dietary sources since the human body totally lacks the enzymatic capacity to synthesize these two EFAs. In contrast, plant cells do have the enzymatic machinery to synthesize LA and ALA such that many plants and derived vegetable oils are abundant sources of both LA and ALA. AA (20:4n-6) is found in small amounts in animal food sources (e.g., eggs and meats) and can also be formed by desaturation plus elongation reactions from its precursor, LA. The long-chain omega-3 fatty acids, DHA and EPA, can be formed to some degree in the human body, albeit to very limited extents as will be discussed later, and can be consumed preformed in the diet from sources rich in DHA/EPA such as fish/fish oils or functional foods which have been enriched or fortified with these important omega-3 fatty acids. Figure 2 shows the metabolic steps (desaturation plus elongation reactions) by which LA is metabolized to AA and by which ALA is metabolically converted to the long chain products including EPA and DHA, the physiologically-essential omega-3 fatty acid for brain and visual functioning. 6 / 8

7 It cells) which phospholipids) particularly relatively consumed available also (retroconversion) Some popular addressed experiments figure, systems levels resulted LA omega-6:omega-3 DHA/EPA fixed recommendations, recommended Canadian that somewhat higher amounts reactions studies pre-formed omega-3 questionable desaturation/elongation concept, reconsidered directly The (AA, and reproduction problematic As cyclo-oxygenase eicosanoids, Figure is mentioned moderately is and noted 2 lowering cells. indicates 20:4n-6) with depicted can is of commentary levels which ALA the 2 press (including dietary based of high for fatty presented be their While and moderately a herein. high efficiency DHA same ALA. where smaller and prostaglandins, readily of the since compared lower product which have previously. dietary acids to the ALA that enhancing preformed throughout EPA the concentrations very approximately Figure LA(n-6):ALA(n-3) Thus, and other back amount. development The dietary level animal initial such considerable enrichment attempts high lowered ratios context accumulates provided rise the EPA limited undergoes of levels. lipoxygenase formed enhanced the cells Figure to omega-6:omega-3 blood processes, metabolized higher dietary reactions 2 to of : levels found 3, marketing delta-6 relative EPA Furthermore, Desaturation, state. studies so-called provides various These higher that AA DHA/EPA those of and even of should This leukotrines samples for from conversion dietary/health 2. intakes initial to can of elevations AA has ALA 10:1 n-6:n-3 and/or tissues desaturation). levels beta to However, by provide animal omega-6:omega-3 to indicated for with cellular/tissue focusing tissues excessively from be of ALA systems) for partly be very to down (omega-6) such the body oxidation various levels of metabolized taken higher desaturation their Health EPA a progression made it potential elongation, such direct of (n-3), and experiments ALA highly body of for most due and concept enrichments. to upon it becoming by corresponding ALA plus situations from a of (as thromboxanes. to that 4:1. DHA intakes and nutritional concentrations giving the to do cells, somewhat tissues Early cellular levels high most dietary efficient to form reduce lipids/phospholipids DHA to LA: reaction. have dependency Subsequent subjects much dotted the Welfare originates undergo by EPA of and plus levels animal ratios interesting fact ALA a rise (e.g., of consumption mitochondria apparent have some diet various due where family plus EPA the elevation retroconversion ALA In supplements lower via elongation that line does better ) ratios of were conclusion, Thus, given products even Canada have 27:1 influenced omega-6:omega-3 very studies DHA. the chronic some which body. (particularly is despite AA primarily of the important much EPA oxygenase ratios human not then that a desaturation/elongation varying found conversion alone, down when not are high competitive of wide lower human reverse note As usually is plus of and figure. of that health these via shown considered of even readily DHA 1990 indicated studies subsequent to revealed needs variety ratios that functions, direct EPA common only dependent products LA:ALA of used moderate n-6:n-3 partially the 3:1) membrane body is enzymes when amount important accumulate omega-6:omega-3 metabolism and conditions. ALA a efficiency where numerous arachidonic referred a early are of inhibitory significant does consumption excessively have of limited which be (tissues EPA. by be ratios ingested consumed human enzyme known suppress such rodent one briefly they of dietary be moderately rise allow indicated (including and long-chain ALA Unlike amount of previous potentially the becomes to human strategy and effect as rise ALA acid as tissues omega-3 ratios, for EPA the was high the of LA a Fig to of polyun 7 / 8

8 Holub, , Wijendran, health. Williams, AA is rheumatoid cells 2) promotion. known important infarctions allow thereby with replacement activity) contrast Figure considered LTB which can Nutrition various and for B.J. as 4, Annu. be 3 reducing products has the tissues, C. PGE role a (heart converted those In V., Clinical arthritis, pro-thrombotic M., chronic Society. partial PUFAs been circulating Rev. to 2, and thrombus products attacks). the of AA associated Hayes, Nutr. nutrition: replacement a EPA disorders psoriasis Burdge, for amount 65:42-50, pro-inflammatory into TXA converted AA : blood 24: , plus Oxygenase-derived neutrophils High formed K.C. formation 2, and 4. G. of respectively. DHA cell with platelets, Omega vaso-constrictory Dietary intakes AA Long-chain the (reduction) mentioned. membranes, into from enhanced do available skin, and (white not the eicosanoid AA n-6 of associated fatty and EPA appear prostaglandin Finally, via and n-3 of is blood to Furthermore cell metabolites inflammatory acids converted AA can plus form PUFA: n-3 eicosanoid proliferation, same cells) associated also fatty DHA have with enzyme-generated cardiovascular plant inhibit aforementioned enzymatic form metabolites acid fatal the (eicosanoids) EPA form thromboxine-a gastrointestinal the v. which balance known potentially with mitogenesis, the marine plus diet, leukotriene-b non-fatal chronic conversion is pathways. DHA, such that though care. and sources. prostaglandin-e from harmful cellular have (via as when myocardial cardiovascular conditions 2 CMAJ. disorders. and (TXA to from AA 4 oxygenase efficiency been play (LTB Proceedings present possibly systems effects (n-6) fish/fish 2) 166: an associated which such 4 In ) of 2 certain which cancer (PGE oils, AA isof 8 / 8