FATTY ACIDS AS BIOCOMPOUNDS: THEIR ROLE IN HUMAN METABOLISM, HEALTH AND DISEASE – A REVIEW. PART 1: CLASSIFICATION, DIETARY SOURCES AND BIOLOGICAL FUNCTIONS

Background. Fatty acids are substantial components of lipids and cell membranes in the form of phospholipids. This review consists of two parts. The present part aims at describing fatty acid classification, dietary sources and biological functions. The second part will focus on fatty acid physiological roles and applications in human health and disease. Results. In humans, not all fatty acids can be produced endogenously due to the absence of certain desaturases. Thus, specific fatty acids termed essential (linoleic, alpha-linolenic) need to be taken from the diet. Other fatty acids whose synthesis depends on essential fatty acid intake include eicosapentaenoic acid and docosahexaenoic acid, found in oily fish. Dietary sources of saturated fatty acids are animal products (butter, lard) and tropical plant oils (coconut, palm), whereas sources of unsaturated fatty acids are vegetable oils (such as olive, sunflower, and soybean oils) and marine products (algae and fish oils). Saturated fatty acids have been related to adverse health effects, whereas unsaturated fatty acids, especially monounsaturated and n-3 polyunsaturated, are thought to be protective. In addition, trans fatty acids have been shown to have negative effects on health, whereas conjugated fatty acids might be beneficial. Lastly, fatty acids are the main components of lipid classes (triacylglycerols, phospholipids, cholesteryl esters, non-esterified fatty acids). Conclusion. Fatty acids are important biocompounds which take part in complex metabolic pathways, thus having major biological roles. They are obtained from various dietary sources which determine the type of fat consumed and consequently health outcome.


INTRODUCTION
Dietary modifications that have occurred over time include changes in the type of fat consumed toward increased consumption of saturated animal fat in particular, and lower intake of unsaturated fat (plant and marine sources) (ref. 1,2 ). This change in the composition of diet may have a great effect on the fatty acid composition of human tissues and affect metabolism and health 3 .
Fatty acids (FA) play multiple roles in humans and other organisms. Most importantly, FA are substantial part of lipids, one of the three major components of biological matter (along with proteins and carbohydrates) (ref. 4 ). Fatty acids are also important energy substrates comprising around 30% of total energy intake for humans. They can be stored in excess amounts in adipose tissue, especially when increased dietary intake of fat and energy occurs resulting in obesity.
Fatty acids are either saturated or unsaturated carboxylic acids with carbon chains varying between 2 and 36 carbon atoms. Polyunsaturated FA (PUFA) are characterized by pentadiene configuration of double bonds. Most FA have an even number of carbon atoms, as they are synthesized from two-carbon units. Specifically, fatty acids are synthesized ad hoc in the cytoplasm from twocarbon precursors, with the aid of acyl carrier protein, NADPH and acetyl-CoA-carboxylase. Their degradation by β-oxidation in mitochondria is accompanied by energy release.
Fatty acid composition is species as well as tissue specific. In animal and plant tissues, the most abundant FA are those with 16 and 18 carbon atoms, i.e. palmitic, stearic, oleic and linoleic. Fatty acids in mammalian organisms reach a chain-length of 12-24 carbon atoms, with 0-6 double bonds. However, fatty acids with chain lengths shorter than 14 and longer than 22 carbon atoms are present only in minor concentrations. Approximately half of the FA in plants and animals are unsaturated and contain 1-6 double bonds.
Fatty acids can be desaturated endogenously up to the Δ9 position due to lack of certain enzymes in humans (Δ12-and Δ15-desaturases). For this reason linoleic (LA; 18:2n-6) and α-linolenic (ALA; 18:3n-3) acids must be taken from the diet and are termed essential. Further elongation and desaturation of these fatty acids to produce long-chain (LC) PUFA, including eicosapentaenoic acid (EPA; 20:5n-3), docosahexaenoic acid (DHA; 22:6n-3) and arachidonic acid (AA; 20:4n-6), is possible but not very efficient in humans. Thus, these fatty acids may be characterized as conditionally essential depending on essential fatty acid availability. Recommendations for minimum dietary intake of EPA plus DHA vary between 250-450 mg/day, especially for pregnant women and those 2 E. Tvrzicka, L.-S. Kremmyda, B. Stankova, A. Zak of reproductive age 5,6 . Rich sources of these LC n-3 PUFA are fish oils and the flesh of oily fish.
From a chemical point of view, lipids are esters of fatty acids with organic alcohols -cholesterol, glycerol and sphingosine. Lipids circulate in the blood stream in the form of lipoproteins, which are composed of cholesteryl esters, triacylglycerols, and phospholipids. Non-esterified fatty acids are bound to plasma albumin. Fatty acids in the form of phospholipids (mainly phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin) form the back bone of all cell membranes and are essential for their fluidity and functionality.
The present review on the role of FA as biocompounds consists of two parts. The first part aims at presenting and discussing FA nomenclature, physicochemical properties, biosynthesis, classification according to saturation, dietary sources, and biological function, as well as the structure and role of lipid classes. The second part of this review (to be published in the next volume of Biomedical Papers) will focus on FA physiological roles and applications in human health and disease as growth and development, cardiovascular health, cancer, and immune system disorders.

FATTY ACID NOMENCLATURE
Fatty acids are carboxylic acids with a typical RCOOH structure, containing a methyl end, a hydrocarbon chain (R) and a carboxylic terminus. Fatty acids have both a systematic and a common name (e.g. octadecanoic and stearic). They are also often expressed as a schematic formula (shorthand notation) as in CN:p n-x, where CN (carbon number) represents total number of carbon atoms, p -number of double bonds, x -position of the first double bond from the methyl terminus (n) (ref. 7 ). For example, the shorthand notation for linoleic acid (9,12-octadecadienoic acid) is 18:2n-6 since it has 18 carbon atoms, and 2 double bonds of which the first one is on the sixth carbon atom counted from the methyl end. A different way of expressing the position of the first double bond is counting from the carboxylic terminus and this is indicated as the Δ position. An example would be that the position of the first double bond in α-linolenic acid (18:3n-3) counting from the carboxylic group is Δ9. The structural formulas as well as types of shorthand notations are shown in (Fig. 1). Important fatty acids 8 involved in metabolic pathways are summarized in (Table 1).

PHYSICOCHEMICAL PROPERTIES OF FATTY ACIDS
The melting point of fatty acids increases with the length of the hydrocarbon chain (i.e. CN), and it decreases with the number of double bonds. This property is also reflected in compounds where FA represent an important component (phospholipids, triacylglycerols), as well as in higher organized structures (plasma membranes, lipoproteins). Under physiological conditions, double bonds preferably have a cis-configuration, which causes a 30° deflection (curve) of the carbon chain. This results in the cis-unsaturated chain occupying greater space, decreasing van der Waals interactions and thus the melting point 9 .
Moreover, the degree of unsaturation (number of double bonds in cis-configuration) significantly influences cell membrane microviscosity and thickness, and consequently also the function of associated proteins (enzymes, cell receptors, membrane transporters and ion channels).
The water solubility of FA decreases as the chain lengthens. In diluted solutions, FA are present as monomers. However, in higher concentrations they form micelles. The concentration, above which FA associate into micelles, is called the critical micellar concentration. In    12 ).

BIOSYNTHESIS OF FATTY ACIDS
Fatty acids are synthesized from two or three carbon precursors, with the aid of acyl carrier protein, NADPH and acetyl-CoA-carboxylase 4 . The elongation is via malonyl-CoA in the microsomal system and acetyl-CoA in the mitochondrial system. Their degradation by  Typically, desaturation of stearic acid (18:0) results in oleic acid (18:1 n-9) and that of palmitic acid (16:0) in palmitoleic acid (16:1 n-7). As shown schematically in (Fig. 3), MFA of the n-9 with 20-24 carbon atoms are elongation products of oleic acid, whereas those of the n-11 family are desaturation and elongation products of arachidic acid (20:0). Further desaturation (Δ6, Δ5) and elongation of oleic acid produces Mead acid (20:3 n-9), which is produced in humans only when dietary intake of essential FA (EFA) is not sufficient 13,14 . Essential FA include LA for n-6 family, and ALA for n-3 family. Essential FA are PUFA which have their first double bond located on the third (n-3 family) or the sixth (n-6 family) carbon atom counting from the methyl terminus of the hydrocarbon chain. Essential FA cannot be synthesized in humans due to lack of Δ12-and Δ15-desaturases which are present only in plants and marine algae 4 , and thus, the human organism is completely dependent on their dietary intake. Further elongation and desaturation of these fatty acids to produce LC PUFA, including EPA, DHA and AA, is performed but not that efficiently in humans. Thus, these fatty acids may be characterized as conditionally essential depending on essential fatty acid availability. The metabolic pathways of EFA are schematically shown in (Fig. 4). It should be noted that fatty acids in individual metabolic pathways differ in their affinity to enzymes and their ability to inhibit desaturases (the FA affinity ratio is n-3 : n-6 : n-9 ~ 10 : 3 : 1).

FATTY ACID CLASSIFICATION, DIETARY SOURCES AND BIOLOGICAL FUNCTIONS
Total fat, as well as the type of fat, determine the effect of their consumption on health 15,16 . Fatty acids can be divided into several groups with respect to their structure, physiological role and biological effects. In the following paragraphs fatty acids are classified according to their structure as saturated and unsaturated.

Saturated fatty acids
Saturated FA (SFA) do not contain any double bonds and can be divided into subgroups according to their chain length: Short chain (saturated) fatty acids (SCFA), include acetic (2:0), propionic (3:0), and butyric (4:0) acids, which are formed during fibre fermentation in the proximal colon. They are quickly absorbed, and acetic and partially also propionic acids are resorbed by portal circulation, transported to the liver and transformed into glucose (propionic acid) and FA (acetic acid). This process can cover 10-20% of resting energy expenditure (REE) Fatty acids as biocompounds: their role in human metabolism, health and disease -a review. Part 1: classification, dietary sources and biological functions  of the human body. Importantly, butyric and partially also propionic acids are used in metabolism, proliferation and restoration (cell replication) of colonocytes.
Other functions of SFA in the colon also include stimulation of: 1) water, sodium, chloride and bicarbonate absorption 2) blood flow through mucous membrane of the colon 3) colonocyte proliferation 4) mucus production 5) limited reproduction of saprophytic bacteria and putrefication due to decreased acidity 17 .
Medium chain (saturated) fatty acids (MCFA) include caproic (6:0), caprylic (8:0), and capric (10:0) acids, which are resorbed directly and transported by the portal vein. Their intramitochondrial transfer does not need the presence of carnitine or carnitine palmitoyl transferases. Fat emulsions containing medium chain triacylglycerols (MCT) are used as nutritional support in enteral nutrition. These have shorter biological half-time and higher stability to lipoperoxidation. These emulsions also inhibit decrease of REE during caloric restriction. Thus they are recommended in some cases of restrictive dietary regimen for obese individuals 18 .
Consumption of saturated LCFA increases levels of cholesterol, namely that of low density lipoprotein (LDL)cholesterol, which is connected with increased coronary heart disease (CHD) mortality 23 . The effect of saturated LCFA in increasing LDL-cholesterol decreases in the direction 12:0 -14:0 -16:0 (ref. 24,25 ). On the other hand, the high density lipoprotein (HDL)-cholesterol lowering effect of saturated LCFA decreases in the direction 14:0-12:0-16:0 (ref. 26,27 ). In contrast, some studies have shown that stearic acid (18:0) decreases LDL-and increases HDL-cholesterol, which may suggest that it has antiatherogenic properties 28,29 . Also, it has been shown   30 . However, it has been suggested that stearic acid has the highest prothrombotic potential compared to other saturated LCFA, although this is under debate 31 . The significance of the increased content of saturated fatty acids in membrane lipid rafts is not yet quite clear 32 .
The atherogenic and thrombogenic potentials of FA can be expressed as atherogenic (AI) and thrombogenic (TI) indices 33 34 . Individuals suffering from these disorders may benefit from administration of n-3 PUFA.

Monounsaturated fatty acids in cis configuration
The cis term is used when the two hydrogens at the double bond are on the same side of the molecule as each other. This leads to a different orientation of the adjoining carbons across the double bond resulting in the molecule having a curved structure. Main representatives in this group are oleic (18:1n-9c), vaccenic 35 (18:1n-7c) and palmitoleic (16:1n-7c) acids. Other MFA synthesized endogenously -myristoleic (14:1n-5c), gondoic (20:1n-9c), erucic (22:1n-9c) and nervonic (24:1n-9c) acids -are present only in minor concentrations. Monounsaturated FA not synthesized de novo include gadoleic (20:1n-11c) and cetoleic (22:1n-11c) acids. Erucic acid, substantial part of noncultivated rapeseed oil (Brassica napus), is suggested to be cardiotoxic 36 . Experiments with erucic acid on rats have shown increased deposition of fat which is followed by the formation of myocardial lesions 37,38 . In human studies, dietary erucic acid was found to reduce the number of platelets and their membrane anisotropy 39 . These findings have initiated the cultivation of rapeseed oil with low content in erucic acid 40 .
Oleic acid (18:1n-9c) has antiatherogenic and antithrombotic properties as it has been shown to increase the HDL-/LDL-cholesterol ratio and decrease aggregation of thrombocytes. Incorporation of oleic acid into cholesteryl esters, triacylglycerols and phospholipids of lipoprotein particles increases their resistance to lipoperoxidation. Replacement of SFA by oleic acid (about 7% of total energy intake (TEI), when total fat is maximum 30% of TEI) decreased concentration of triacylglycerols (TAG), LDL-cholesterol, and increased concentration of HDL-cholesterol, and regulated insulin sensitivity 41 . Olive oil has also been tested experimentally for its protective role in carcinogenesis 42 and for its effect on the inflammatory response 43 21 . (Table 3) shows the percentage of individual FA for oils rich in MFA (ref. 22 ).

Monounsaturated fatty acids in trans configuration
These are molecules that have one double bond in which the hydrogens are on the opposite side to one another resulting in a non-curved structure and thus, to physicochemical properties close to those of SFA, affecting cell membrane properties similarly to SFA. Main trans MFA are elaidic (18:1n-9t) and trans-vaccenic (18:1n-7t) acids. Trans FA are of exogenous origin. Their atherogenic effect 44 is assumed to be greater than that of SFA. Also, trans MFA are twice as active in raising LDL-cholesterol and decreasing HDL-cholesterol than SFA. The different effects of trans FA and SFA on human metabolism are still being studied 45,46 . Main dietary sources of trans FA are hardenings or shortenings (such as margarines from hydrogenated plant oils using an improper catalyst) and butter (trans FA in milk originate from the gastrointestinal tract of ruminants). Hydrogenated fats are used mainly in pastry and the "fast-food" industry 47 . However, advances in technology used by the food processing industry have now reduced the production of trans fatty acids.

Polyunsaturated fatty acids
Polyunsaturated FA contain two or more double bonds in the molecule. In general, the more double bonds there in the fatty acid, the more prone they are to lipoperoxidation 48 . Endogenous PUFA mostly belong to the n-9 family, synthesized in increased amounts when there is a lack of EFA (LA, ALA) (ref 49 ). These FA are termed essential because they cannot be synthesized de novo in humans and they are considered parental FA for the n-3 and n-6 PUFA families 50 . Essential FA exert beneficial antiatherogenic as well as antithrombotic effects. This is a result of their impact on lipoprotein concentration, membrane fluidity, function of membrane enzymes and receptors, modulation of eicosanoid production, regulation of blood pressure and metabolism of minerals 51 .

n-3 Polyunsaturated fatty acids
In the n-3 PUFA family the parent fatty acid is ALA. Its main metabolic products are EPA (timnodonic acid) and DHA (clupadonic acid), and to a lesser extent docosapentaenoic acid (DPA, 22:5n-3). These metabolites are termed LC n-3 PUFA. Dietary sources of ALA are seeds and leaves of some plants -soybeans (Glycine max), linseed (Linum usitatissimum), blackcurrant seeds (Ribes nigrum) and borage leaves (Borago officinalis), as well as their oils 21 . Its metabolites, EPA and DHA, can be taken from the diet through oily fish which are excellent sources containing approximately 2 g of EPA plus DHA per portion of fish (150 g). Among other fish, oily fish include sardines, mackerel, trout, salmon, fresh (not canned) tuna, and herring. Other sources of LC n-3 PUFA include fish oils, the liver of non-oily fish (such as cod and haddock), and the flesh of some white non-oily fish but in much lower amounts 5 . Conversion of ALA into 20-22 CN metabolites is much more effective in marine animals than in human species. Thus, EPA and DHA are in humans mostly of exogenous source 52,53 . The high content of DHA in nervous tissues and the retina is extremely important. Also, the unique properties of this FA play a role in the mechanism of signal transduction, probably by regulation of G-protein signaling 54,55 .
As ligands of peroxisome proliferator-activated receptor (PPAR-α), n-3 PUFA have a number of pleiotropic effects on lipid and energy metabolism. They are thought to activate PPAR-α and decrease lipogenesis and very low density lipoprotein (VLDL) secretion 56 by suppression of sterol response element binding protein (SREBP-1). Also, other potential effects of n-3 PUFA are to increase the activity of lipoprotein lipase, decrease concentrations of apo C-III and potentiate reverse cholesterol transport 57,58 . In the form of high concentration oil supplements, n-3 PUFA are thought to induce expression of uncoupling proteins (UCP) and increase density of mitochondria by β-oxidation of FA in muscles [59][60][61][62] . The immunomodulative properties of LC n-3 PUFA are connected with their ability to suppress the activation of T-lymphocytes 63 . This activation demands acylated proteins, localized in cell membrane lipid rafts, which leave the raft after increased exposure to (and thus content of) LC n-3 PUFA (ref. 57,64 ).
Polyunsaturated FA of the n-6 family are activators of PPAR (γ > α). Their metabolic effects include affecting cytokine production 65 , increased cholesterol synthesis, increased activity of LDL-receptors resulting from increased mRNA for LDL-receptors, increased activity of cholesterol 7α-hydroxylase (Cyp 7A1) and decreased conversion of VLDL to LDL (ref. 66 ). Supplementation with n-6 PUFA leads to decreased total, LDL-and HDLcholesterol and increased sensitivity of LDL particles to lipoperoxidation. This effect is a result of the "upregulation" of LDL-receptors and the activity of Cyp 7A1. As ligands of PPAR-γ, n-6 PUFA increase insulin sensitivity, change the distribution of fat and the size of Fatty acids as biocompounds: their role in human metabolism, health and disease -a review. Part 1: classification, dietary sources and biological functions  Borage  seed  1 2 : 0  ------------1 4 : 0  ------------ adipocytes 67,68 . Importantly, AA is a major precursor of eicosanoids which are potent signalling molecules both inside and outside the cell 69 .

Conjugated fatty acids
As mentioned above, most PUFA are characterized by pentadiene configuration (i.e. methylene interruption) of the double bonds, with the exception of conjugated FA. Most abundant FA with a conjugated system of double bonds are isomers of LA (conjugated linoleic acid; CLA). These FA appear in red meat and dairy products; cows grazing pasture have a several times higher content of CLA in meat and milk fat than cows fed typical dairy diets. There are 28 possible isomers of CLA, which differ in the position (e.g. 7 and 9, 8 and 10, 9 and 11, 10 and 12, 11 and 13 -counting form the carboxyl group) and configuration (cis or trans) of double bonds. The type most commonly found in meat and dairy products is rumenic acid (18:2Δ9c,11t). Also, the isomer 18:2Δ10t,12c has important metabolic effects 70 . Compared to previous generations, the current human population consumes less CLA in their diet preferring white to read meat and very low fat dairy products. Thus, CLA, containing equal amounts of 18:2Δ9c,11t and 18:2Δ10t,12c isomers, is frequently used as special dietary supplement.
The origin of conjugated FA is similar as that of trans FA. However, their biological effect is mostly positive 71,72 . Conjugated FA are shown to have both in vitro and in vivo antioxidant properties (probably due to the production of FA with furan structures) and anticarcinogenic effects. Paradoxically, an anti-cancer effect of beef products was found in a study which included fried meat 73,74 . The isomer 18:2Δ10t,12c inhibited fat accumulation in vivo, while the isomer 18:2Δ9c,11t improved parameters of lipid metabolism affecting expression of SREBP-1c and liver X receptor α (ref. 75,76 ). However, conflicting results have been obtained from animal and human studies 77 . Further studies focusing on the effects of different CLA isomers would help to resolve some of these issues.
Lipids circulate in the bloodstream assembled along with proteins into large, soluble structures termed lipoproteins. Circulating lipids (in the form of lipoproteins) consist of cholesteryl esters (CE; 60-70% of total cholesterol) and TAG situated in the non-polar core of lipoproteins, and phospholipids (mainly phosphatidylcholine and sphingomyelin) and free cholesterol in the polar envelope. Non-esterified fatty acids (NEFA; product of lipolysis and source for lipid synthesis) are bound to plasma albumin 79 .
Cholesteryl esters represent the transport and storage form of cholesterol in the organism; at the temperature of the interior media they form liquid crystals. Cholesteryl  Triacylglycerols are the main core components of VLDL and chylomicrons, as well as lipid inclusions of adipocytes. The most abundant FA in TAG is oleic acid (40%) followed by palmitic (22%) and linoleic (20%) acids 81 . A similar content of FA was also found in adipose tissue: oleic acid -50%, palmitic acid -22% and linoleic acid -12%, since TAG are formed, partially, by FA released from adipose tissue which are representative of its content. Fatty acids as biocompounds: their role in human metabolism, health and disease -a review. Part 1: classification, dietary sources and biological functions Phospholipids (PL) are along with cholesterol the main lipids of the lipoprotein envelope and represent polar (hydrophilic) lipids. Molecules of PL are freely exchanged not only between individual lipoproteins, but also between the lipoprotein envelope and plasma membranes. This process is facilitated by specific transfer proteins. The composition and content of individual PL in the lipoprotein envelope is similar for the main lipoprotein classes, with the exception of chylomicrons. The most buoyant phospholipid class is phosphatidylcholine (PC, lecithin), whose content in plasma reaches 60-70%, followed by sphingomyelin (SM, 10-20%), lysolecithin (LPC, 3-5%) and phosphatidylethanolamine (PE, 2-6%). Minor phospholipids in plasma are phosphatidylserine (PS, 1-2%) and phosphatidylinositol (PI, 1-2 %). In plasma PC the dominating FA is palmitic acid (30%), followed by linoleic (25%), stearic (14%), oleic (11%) and arachidonic (11%) acids 80 . Plasma phospholipid FA content reflects in approximation that of cell membrane phospholipids and it thus may be characterized as the "functional" lipid pool. The FA profile of the main plasma lipid classes of healthy individuals is shown in (Table 5) (ref. 82 ).
Membrane lipids, which ensure fluidity and functionality, consist of PC, PE, SM and minor phospholipids (PS, PI, LPC and lysophosphatidylethanolamine-LPE). The fatty acid content in individual lipid classes influences substantially the membrane fluidity 12 . The two most abundant phospholipids in cell membranes are PC and PE, both predominately with palmitic acid and rich in PUFA. Usually PE has a higher content of PUFA. The head groups of phospholipids affect the membrane biochemical properties; some organelles may have much more PE than the cell membrane which is higher in SM. Moreover, the content of individual phospholipids in membranes and their fatty acid composition are species as well as tissue specific; liver cell membranes are high in PC, brain cell membranes are high in gangliosides, but bacterial membranes contain mostly PE.
Non-esterified FA are present in plasma under physiological conditions only in minor concentrations (0.5-1.0 mmol/l), their profile is similar to that of TAG and of adipose tissue, since they are released during TAG hydrolysis in adipocytes 83 . Non-esterified FA can be oxidized, reesterified, or metabolized (elongation and desaturation). During physical activity they are oxidized in muscles, whereas during resting periods they are oxidized in the liver and myocardium. Most NEFA are re-esterified in the liver to TAG and phospholipids. A limiting step for the mobilization of NEFA from adipose tissue to plasma is the activity of the responsible enzyme, hormone-sensitive lipase. An increased concentration of NEFA is toxic, affecting plasma membranes and resulting in arrhythmias, thrombogenesis etc. Together with increased glucose concentration, NEFA may accelerate the formation of the reactive oxygen and nitrogen substances (RONS), as well as initiation and development of endothelial dysfunction. Lastly, some partial esters -monoacylglycerols (MG), diacylglycerols (DG), LPC and ceramides -are intermediate products of the synthesis or degradation of other simple as well as complex lipids. Their content in plasma is very low; some of them as second messengers (DG, inositoltriphosphate -IP 3 ) can regulate a wide range of cell activities. The fatty acid composition in these minor lipids reflects that of parent lipid classes.

CONCLUSION
The first part of this review on FA as biocompounds presented their classification and dietary sources, as well as the complex metabolic pathways that FA are involved in. Fatty acids in the form of phospholipids are major components of cell membranes, affecting their structure and fluidity. The degree of FA unsaturation and chain length determine the physicochemical properties of FA, and thus the functionality of cells and tissues as well as lipid mediators produced. Fatty acids can be desaturated endogenously up to the Δ9 position due to lack of certain enzymes in humans. For this reason LA and ALA must be taken from the diet and are termed essential. Further elongation and desaturation of these fatty acids results in LC PUFA, including EPA, DHA, and AA. However this process is not very efficient in humans and, thus, these FA may be termed conditionally essential. Dietary FA (in the form of TAG) are a major source of energy and determine the fatty acid composition of cell membranes and tissues. The type of fat consumed depends on the dietary sources, typically including saturated fat from animal sources and tropical plant oils (coconut, palm), and polyunsaturated fat from vegetable oils (such as olive oil for MFA; sunflower oil and soybean oil for n-6 PUFA; flaxseed oil for n-3 PUFA) and marine sources (algae and fish oils for LC n-3 PUFA). Saturated FA have been connected to adverse health effects, whereas unsaturated FA are thought to be more beneficial for human health. Specifically MFA and n-3 PUFA are characteristic for their protective role, as opposed to n-6 PUFA, with a special focus on LC n-3 PUFA (EPA, and DHA). In addition, trans FA have been shown to have negative effects on health, whereas conjugated FA (such as CLA) have been shown to have beneficial effects which should be further investigated. Lastly, a major role of fatty acids is being the main constitutional components of lipid classes, including TAG, PL, CE and NEFA. The second part of this review to follow will focus on the role of FA in health and disease, including the current literature on FA physiological roles and practical implications for specific conditions.