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Introduction to Essential Fatty Acids

Alok Patel*, Ulrika Rova, Paul Christakopoulos and Leonidas Matsakas

Biochemical Process Engineering, Division of Chemical Engineering, Department of Civil, Environmental, and Natural Resources Engineering, Luleå University of Technology, Luleå, Sweden

Abstract

Certain omega-3 fatty acids, such as a-linolenic acid (ALA), and omega-6 fatty acids, such as linoleic acid (LA), cannot be synthesized in the human body and are recognized as essential fatty acids. While some long-chain polyunsaturated fatty acids (LC-PUFA) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can be synthesized from the parent omega-3 fatty acids (ALA), this is done at a very low conversion rate, hence it must be taken through diet to fulfill the daily intake requirement. Both EPA and DHA have several vital activities in the human body, such as anti-inflammatory effects and being the structural component of the cell membrane. The fatty acids DHA, arachidonic acid (AA), and LA accumulate most usually in tissues, whereas DHA mostly accumulates in retina and brain gray matters and it is important for proper visual and neurological development during gestation period and postnatal period. Replacement of saturated fatty acids with omega-3 and omega-6 fatty acids in daily diet reduces the risk of cardiovascular disease and prevents diseases such as Alzheimer's, bipolar disorder, and schizophrenia. Proper EPA and DHA content also help individuals with type 2 diabetes to reduce the elevated serum triacylglycerides. It also facilitates infants to reduce the risks of fatal myocardial infarction and other cardiovascular diseases. Hence, as recommended by the American Heart Association, it is necessary to consume fish, and especially oily fish at least twice per week as it is an excellent source of these fatty acids. Marine fishes of Salmonidae, Scombridae, and Clupeidae families are important sources of omega-3 fatty acids but due to the increasing demand of PUFA and diminishing aquatic ecosystem, fishes are not a sustainable source to serve as a long-term feed-stock for omega-3. Plants can synthesize some of PUFA such as oleic acid, LA, GLA (?-linolenic acid), ALA, and octadecatetraenoic acid but due to lacking some essential enzymes for PUFA synthesis such as desaturase and elongases, they are incapable of synthesizing EPA and DHA. Oleaginous microalgae and thraustochytrids could be a sustainable option to produce microbial EPA and DHA.

Keywords: Oleaginous microorganisms, lipid accumulation, fatty acid profile, microalgae, nutraceuticals, omega-3 fatty acid, human health

1.1 Introduction

Fatty acids or lipids serve in diverse metabolic functions related to growth and maintenance of cells and tissues, and act as caloric energy molecules involved in various cellular signaling events that accompany several physiological processes after metabolism [1, 2]. Lipids are usually originated from the acetate route and derivatives of polyketides [3]. Chemically lipids are hydrocarbons of C6 to C32 long-chain, containing hydrophilic carboxyl group at one end and methyl group at the terminal end. These hydrocarbon chains are made up of an even number of carbon atoms in naturally occurring fatty acids; however, they can be branched or cyclic that is present in some bacterial strain [3]. The hydrocarbon chain can be saturated, mono-unsaturated or polyunsaturated depending on the presence and numbers of double bond [4, 5]. From the different fatty acid types, polyunsaturated fatty acids (PUFAs) have greater physiological importance because of their medicinal properties [6]. Omega-3 and omega-6 fatty acids belong to a category of PUFAs where the first double bond is located between the 3rd and 4th carbon atom near the methyl end (or omega end) of omega-3 fatty acids (n-3) whereas the first double bond is situated between the 6th and 7th carbon in the case of omega-6 fatty acids (Figure 1.1).

Figure 1.1 The chemical structure of DHA and EPA, representative omega-3 and omega-6 PUFAs.

Figure 1.2 Molecular structure of omega-3 fatty acids and omega-6 fatty acids.

These fatty acids have unique structures due to the presence of the double bond as it introduces the bends in the hydrocarbon chain which affect its physical properties (Figure 1.2) [7]. Mammals can synthesize saturated and unsaturated fatty acids from carbon present in carbohydrates and proteins while they show an inability to synthesize PUFAs due to the lack of certain enzymes that are necessary to introduce the cis double bonds at n-3 and n-6 position [5]. These omega-3 and omega-6 fatty acids are considered as essential fatty acids for human beings and must be taken through diet. a-linoleic acid (ALA, 18:3n-3) and linoleic acid (LA, 18:2n-6) are the parent fatty acids of omega-3 and omega-6 fatty acid series, respectively [4].

Humans can synthesize long-chain PUFA (LC-PUFA) such as eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), from ALA and dihomo-?-linolenic acid (DGLA; 20:3n-6) and AA (20:4n-6), from LA. Some investigators showed that only 2 to 10% of ALA can be converted into EPA and DHA [8], while others suggested that 7% of ALA is converted into EPA while low conversion rate (0.013%) is reported for DHA [9]. Hussein et al. (2005) suggested that only 0.3% of EPA and <0.01% of DHA can be converted from ALA [10]. The conversion of ALA to EPA and DHA is too low and cannot meet the daily intake requirement. These fatty acids have several health benefits as they are incorporated in various parts of the body including cell membrane and play a vital role in anti-inflammatory process [11, 12]. Both EPA and DHA are essential for proper aging and fetal development [13], DHA is mainly incorporated in the retina and brain. They are also used to treat and prevent several viral diseases.

1.2 Biosynthesis of PUFAs

Fatty acids are absorbed in intestines after hydrolysis from dietary fats (tri-acylglycerols and phospholipids) by pancreatic enzymes [14]. Micelles are formed in intestines after mixing fatty acids and other fat digestion products in the presence of bile salts. Fats are absorbed to an extent of 85-90% throughout the small intestine from these mixed micelles [14]. Omega-3 fatty acids are considered as essential fatty acids as they cannot be synthesised by humans and animals, due to lack of the ?-12 and ?-15 desaturase enzymes [4, 5]. As humans and animals are unable to produce a de novo synthesis of omega-3 fatty acids, these must be taken through their diet from other sources [15]. However, they have the capability to synthesise small amounts of DHA and some intermediate products such as EPA from the parent omega-3 fatty acids such as ALA, and the rest of the required amount is fulfilled from direct consumption of DHA and EPA [16]. The parent ALA intake is done also through our diet from plant sources. The metabolism starts by the action of ?-6 desaturase on ALA, for the unsaturation in aliphatic carbon chain, followed by the addition of two carbon atoms in the aliphatic carbon chain by the action of elongases. This structure of fatty acids allows the action of ?-5 desaturase and finally formation of EPA [16]. Some previous studies showed that a desaturation process occurs in endoplasmic reticulum [16]. However, the role of ?-4 desaturase was established from the microbial pathway for DHA synthesis (22:6?-3) from 22:5?-3. This part of the pathway was interpreted after the discovery of 24:5?-3 from the elongation of 22 carbon chain and further desaturated into 24:6?-3 in the mammals [17] and there is a reverse pathway of partial oxidation of 24:6?-3 to synthesize DHA in peroxisomes [18]. This is also evidenced by the treatment of peroxisomal disorders, such as Zellweger syndrome, in infants by dietary supplementation of DHA [19]. The unsaturation and elongation process during synthesis of fatty acids is presented in Figure 1.3.

There is another pathway of fatty acid synthesis that was discovered in the thraustochytrids strain Schizochytrium sp. and is known as polyketide synthesis pathway (PKS). This pathway is distinguished from the conventional Fatty acid synthesis (FAS) pathway in terms of oxygen requirements, as it does not require molecular oxygen for the synthesis of PUFAs [23]. In this microorganism, C14 and C16 fatty acid synthesis follows the FAS system, while the synthesis of LC-PUFA follows the PKS pathway [24]. A major difference between the FAS and PKS pathways is that the elongation of fatty acids is done through dehydration and isomerization of fatty acyl intermediates in the PKS pathway, whereas in the FAS pathway it occurs through elongases and desaturases [25]. Although LC-PUFA synthesis in thraustochytrids is not fully understood yet, the identification of a ?-4 fatty acid desaturase in thraustochytrids indicated that DHA synthesis might be a result of the FAS pathway [23]. In FAS route of PUFA synthesis, a series of desaturases and elongases works on either the C16:0 or C18:0 to form unsaturated fatty acids and DHA is synthesized from 22:5 by delta-4 desaturase [24]. It has been proved by genome annotation results of thraustochytrids S. limacinum that this microorganism does not have delta-4 desaturase as reported in FAS...