This class of fatty acids is characterized by an even-numbered aliphatic chain starting from a carboxylic carbon and ending in a methyl group. The structure possesses two or more all-cis double bonds (polyunsaturated), the first of which is located three or six carbons away from the methyl (omega) carbon, hence the name, omega-3 and omega-6 polyunsaturated fatty acids (PUFA).
They are also components of the phospholipid bilayer which envelope cells and organelles and are converted to other molecules such as eicosanoids including prostaglandins, thromboxanes, leukotrienes and other molecules implicated in immune reactions and signals. Also because of their health implications, they are subject of many research studies which aim to improve certain medical conditions, finding alternative sources and determining the optimum amounts in the diet for maximized health benefits.
Lipids are a diverse class of biomolecules that are distinguished from the other classes because of their solubility in non polar solvents. This is due to the relatively large hydrophobic portion, usually consisting of an aliphatic hydrocarbon chain or ring attached to other functional groups. Being derivatives of carboxylic acids, they can undergo the same reactions typical of carboxylic acids. Thus, they may combine with alcohols to produce acyl compounds called esters. This very reaction allows for a diverse array of lipid structures.
They find use as components of the cellular membranes aiding in protection and fluidity of the lipid bilayer; for energy storage because of their oxidation potential, because of this, they generate ample amounts of heat during fat burning; as body insulator because fat is a poor conductor of heat and prevents heat loss through the skin; as tools for molecular recognition between attached moieties (usually proteins) and the hydrophobic environment and protective covering of tissues among others.
This large group is classified based on their structure as follows: (a) fatty acids and derivatives, (b) triacylglycerols, (c) wax esters, (d) phospholipids, (e) sphingolipids, and (f) isoprenoids (1). Triacylglycerols are esterification products of glycerol and three fatty acids. They are important components of adipose cells and are generally used as energy reserves. These molecules can undergo saponification reactions which produces carboxylate salts of soap.
Phospholipids are the major structural components of membranes and find use as emulsifiers and surfactants due to the presence of a small polar head represented by the charged phosphate group. They may also be used as protective coverings of small molecules and probiotics (2). Wax esters are important components of leaves, fruit and animal fur. They may be combinations of many types of functional groups such as alcohols, aldehydes and sterols. Sphingolipids are hydrophobic amino alcohols which are generally found composing animal membranes.
It is also found covering the myelin sheath of neurons and assists in the transmission of messages in the brain. The isoprene ring is characteristic structure of isoprenoids. They are distinguished from other lipid classes by a five carbon unit, methylbutadiene. Examples of this class include essential oils which are mixtures of terpenes giving fruits and flowers their characteristic scent; carotenoids which are plant pigments that have the structure of tetraterpene, vitamin E, vitamin K, ubiquinone and some hormones (1).
The omega-3 and omega-9 polyunsaturated fatty acids (PUFA) are very important examples of lipids belonging to the first group. Examples of this class are aptly called essential fatty acids because these molecules need to be supplemented in the diet since our body lacks the enzymes for its synthesis. These include the short chain PUFA which are in turn precursors of other long chain omega-3 and omega-9 PUFA. Fatty acids that can be synthesized in by the body because of existing pathways and enzymes are referred to as non essential fatty acids (3).
This paper discusses the structure of omega-3 and omega-6 fatty acids, their biochemical functions, products and applications especially in maintaining good health and tackles current discoveries regarding their transformation to new molecules, issues concerning increased dietary intake and health prospects. Nomenclature and structure Fatty acids are synthesized in the liver and adipose cytoplasm through the fatty acid synthase and malonyl CoA a precursor. The chain increases by two carbons at each round of the reaction catalyzed by a unique enzyme complex until it forms a saturated fatty acid containing 16 carbons (palmitic acid).
Through a series of elongation, reduction, dehydration and desaturation reactions various types of unsaturated fatty acids are produced. The reaction can incorporate double bonds up to the ninth carbon in mammalian system since the required enzymes are lacking and so we depend on plant sources for these essential fatty acids (3). Omega-6 polyunsaturated fatty acids Fatty acids are called such because of the attachment of a long hydrophobic tail made of an aliphatic chain to a carboxylic acid functional group.
This carboxylic carbon is referred to, in nomenclature, as the ? carbon. The chain is terminated by a methyl group assigned as the ? position. Polyunsaturated fatty acids are characterized by the presence of conjugated alkene groups in the cis confirmation. Thus, the position of the double bond can be indicated from the carboxylic carbon or from the methyl end. Thus, linoleic acid, a fatty acid with eighteen carbons and with two double bonds at carbons 9 and 12 from the carboxylic end can be designated as 18:2? 9,12.
The dietary profile of the intake of fatty acids also determines the fatty acid composition of the phospholipid double layer. The latter can be assessed by determining the profiles of lipids from erythrocytes and plasma lipids, as well as identifying the membrane fluidity using analytical techniques (5). Another method of measuring membrane fluidity includes the use of various fluorescent markers which can tag protein molecules that are embedded in the lipid bilayer. The tendency of the colored markers to mix depends on the ability of the proteins to move through the membrane as time passes.
The FRAP method, fluorescence recovery after photobleaching, can also be related to the fluidity of membranes since it can measure lateral diffusion. This technique takes advantage of the ability of laser to bleach a pre marked fluorescent portion. As the membrane moves, color is regained and visualized using video equipment. Probes attached to the membrane can also be detected by nuclear magnetic resonance (NMR) spectroscopy (1). Arachidonic acid is also an important fatty acid component of phospholipids. The high degree of unsaturation ensures that the lipid bilayer is flexible and fluid even at slightly lower temperatures.
The characteristic four conjugated double bonds prevent solidification at physiological temperatures and typically undergo alkene reactions such as oxidation. Its pKa is also suited to regulate its solubility in the aqueous and hydrophobic portions of the cell. In the salt form, it can be solvated by water but reverts back to its hydrophobic form once the salt reacts with free H+ in solution (6). Eicosanoid synthesis Omega-3 and omega-6 polyunsaturated fatty acids are also synthetic precursors of autocrine regulators called eicosanoids.
Arachidonic acid is central to many pathways in the production of eicosanoids. These arachidonic acid-derived molecules, which include prostaglandins, thromboxanes and leukotrienes, are difficult to analyze because of their limited concentrations and short periods of activity. The molecules are usually released as a response to immune reactions triggered by infections and antigen attack (1). In addition, they trigger molecular cascades which can affect even the expression of lipid metabolizing enzymes and present perils in metabolic disorders (7).
The eicosanoid synthesis is mediated by two groups of enzymes and is achieved through the pathways utilizing cyclooxygenase, lipoxygenase (8). Prostaglandins feature a cyclopentane ring in its structure with alcoholic functional groups at carbons in position eleven and fifteen. They are named as PGXy (prostaglandins) classified according to letters (symbolized by X) while y (subscript) indicated the number of double bonds found in the structure. Different letter classes are indicated by similarities in the functional group attached to the core structure but the group derived from arachidonic acid is one of the most significant.
They are important molecules that signify inflammation reactions during infection and pain and are involved in muscular contractions during birthing events and ovulation. Apparently, they also have varying roles depending on the type of cell and tissue where they are produced (1). In fact, both omega-3 and omega-6 PUFA find importance in the synthesis of prostaglandins. The products from each, however, have different actions. Prostaglandins resulting from omega-3 PUFA have anti-inflammatory functions, while that synthesized from omega-6 are inflammatory.
Thus, the ratio of omega-3 and omega-6 fatty acids is important because these molecules compete for the same enzymes and the synthesis products should complement each other (9). Thromboxanes are cyclic ether derivatives of eicosanoids whose name can be symbolized as TXZy. Z represents the class of thromboxane and y indicates, as in the case of prostaglandins, the number of double bonds. They are involved in platelet aggregation and vasoconstriction. Leukotrienes, on the other hand, are eicosanoid molecules originally isolated from white blood cells, hence the name.
They are also classified according to groups symbolized by letters (X) and subscripts (y) denote the number of double bonds found in the structure (LTXy). They are also implicated in processes involving inflammation, bronchoconstriction, vasoconstriction and capillary permeability (1). The overexpression of cyclooxygenase and lipooxygenase enzymes which oxidize the double bonds of arachidonic acid to form eicosanoids has been implicated in possible tumorigenesis in the human brain such as in gliomas and meningiomas.
Thus, their structures are used as models for designing drugs that target inhibitory sites on the enzymes. It is predicted that future medicines that aim to cure brain tumors may be based on blocking certain reactions catalyzed by cyclooxygenases and lipooxygenases in the eicosanoid synthesis pathway (8). Due to its importance in brain, eyesight development, physical and behavioral functions, alternative sources of these omega-3 PUFA are being tapped and utilized to produce fortified food. Arterburn et al. 2007) have assessed the possibility of utilizing algae as sources of these important fatty acids and found substantial amounts of synthesized arachidonic acid, docosapentaenoic acid and eicosapentaenoic acid in membrane lipids and blood cells using algal oil fortified capsule supplements and foods (10).
Health benefits and issues Early studies in animals and human test subjects have already established the important roles that omega-3 and omega-6 polyunsaturated fatty acids play in health functions. A study by Carlson et al. 2003) reports that diets deficient in omega-6 fatty acids impairs the growth of infants by decreasing the synthesis of arachidonic acid whose products play roles in development and phospholipid synthesis (11). It was recently identified that brain lipids metabolism and synthesis has a large dependence on levels of omega-3 and omega-6 PUFA, specifically docosahexaenoic acid and other eicosanoids (12). The diet of infants can easily be devoid of omega-3 and omega-6 essential fatty acids, interestingly, it was observed that these fatty acids are transmitted to the fetus from the pool of nutrients of the mother.
It is thus important to maintain balance of these fatty acids in lactating and pregnant mothers for the proper development of their infants (5). The role of omega-3 and omega-6 PUFA in the development of brain disorders such as schizophrenia is also attributed to the ability of these fatty acids to inhibit the phospholipid degrading enzyme phospholipiase A2 which is found to be increased in schizophrenic individuals (7). Various studies have also reported the beneficial effects of an omega-3 and omega-6 rich diet on physical, behavioral and even psychological health.
On the contrary, Hakkarainen et al. 2004) monitors the effect of an increased omega-3 and omega-6 fatty acid intake and reports that a positive correlation is observed towards anxiety, alcoholism and depression among male subjects (13). The relation of diseases which stem from genetic alterations such as cancer and their risks based on profiles of dietary intake of omega-3 and omega-6 PUFA are also being established. It has been observed that omega-3 polyunsaturated fatty acids lessens the odds of acquiring prostate cancer by slowing down the growth of prostate tumor cells but is reversed by omega-6 polyunsaturated fatty acids.
Similarly, inter conversion of omega-6 to omega-3 PUFA re-established the positive effects of omega-3 on prostate cancer (14). These reports acknowledge that a healthy diet can be used to minimize genetic predispositions to certain diseases. In addition, if coupled with a healthy diet, preventive lifestyle measures, adequate nutrients, avoidance of red meat, refined floor products and concentrated sugars, substantial sulforophane rich foods such as allium and broccoli, intake of minerals, folic acids, vitamins, antioxidants, carotenoids, probiotics and dietary supplements, these measures and precautions can ward of the risks of cancer (15).