**6. Isomerism of fatty acids**

8 Lipid Metabolism

notation

**5. Essential fatty acids** 

triacylglyceride, specifying the "sn-" notation.

triacylglycerides, its carbon atoms are not chemically and structurally equivalent. Thus, carbon 1 of the glycerol is referred as carbon (α), or sn-1 (from "stereochemical number"); carbon 2 is referred as carbon (β), or sn-2, and carbon 3 as (γ), or sn-3. It is important to note that the notation "sn" is currently the most frequently used [37]. This spatial structure (or conformation) of mono-, di- and triacyglycerides is relevant in the digestive process of fats and oils (ref). Figure 2 shows the structure of a monoacylglceride, a diacylglyceride and a

**Figure 2.** Structure of a monoacylglyceride, a diacylglyceride and a triacylglyceride, specifying the "sn-"

The capability of an organism to metabolically introduce double bonds in certain positions of a fatty acid or the inability to do this, determines the existence of the so-called nonessential or essential fatty acids (EFAs). According to this capability, mammals, including primates and humans, can introduce a double bond only at the C9 position of a saturated fatty acid (according to "ω" nomenclature) and to other carbons nearest to the carboxyl group, but not at carbons nearest the C1 position [38]. This is the reason why OA is not an EFA. In contrast, mammals can not introduce double bonds at C6 and C3 positions, being the reason why AL and ALA are EFAs. By derivation, the AA is formed by the elongation and desaturation of LA, and EPA and DHA, which are formed by elongation and desaturation of ALA, become also essential for mammals when their respective precursors (LA and ALA, respectively) are nutritionally deficient [39]. Figure 3 shows the chemical According to the distribution of double bonds in a fatty acid and to its spatial structure, unsaturated fatty acids may have two types of isomerism: geometrical isomerism and positional isomerism. By isomerism it is referred to the existence two or more molecules having the same structural elements (atoms), the same chemical formula and combined in equal proportions, but having a different position or spatial distribution of some atoms in the molecule [40].

### **6.1. Geometrical isomers of fatty acids**

Carbon atoms forming the structure of the fatty acids possess a three-dimensional spatial structure which forms a perfect tetrahedron. However, when two carbons having tetrahedral structure are joined together through a double bond, the spatial conformation of the double bond is modified adopting a flat or plane structure [41]. Rotation around single bonds (C**-**C) is entirely free, but when they are forming a double bond (C**=**C), this rotation is impeded and the hydrogen atoms that are linked to each carbon involved in the bond may be at the same side or opposed in the plane forming the double bond. If hydrogen atoms remain at the same side, the structure formed is referred as *cis* isomer (denoted as "*c*"). When hydrogen atoms remain at opposite sides the structure formed is referred as *trans* isomer (denoted as "*t*", *trans*: means crossed) [42]. Figure 4 shows the *cis* – *trans* geometric isomerism of fatty acids. The *cis* or *trans* isomerism of fatty acids confers them very different physical properties, being the melting point one of the most relevant [43]. Table 2 shows the melting point of various *cis* – *trans* geometric isomers of different fatty acids. It can be observed substantial differences in the melting point of *cis*- or *trans* isomers for the same fatty acid. Melting point differences bring to the geometrical isomers of a fatty acid very different biochemical and nutritional behavior. Fatty acids having *trans* isomerism, especially those of technological origin (such as generated during the partial hydrogenation of oils), have adverse effect on humans, particularly referred to the risk of cardiovascular diseases [44]. It is noteworthy that the majority of naturally occurring fatty acids have *cis* isomerism, although thermodynamically is more stable the *trans* than the *cis* isomerism, whereby under certain technological manipulations, such as the application of high temperature (frying process) or during the hydrogenation process applied for the manufacture of shortenings, *cis* isomers are easily transformed into *trans* isomers [45].

Overview About Lipid Structure 11

isomers (oleic acid *cis* and vaccenic acid *trans*) and at the same time positional isomers, since oleic acid has a double bond at the Δ9 position and vaccenic acid at the Δ11 position [46].

**Fatty acid Isomerism Melting point (°C)** C12:0 ------ 44.2 C16:0 ------ 62.7 C18:0 ------ 69.6 C18:1 Cis 13.2 C18:1 Trans 44.0 C18:2 cis, cis -5.0 C18:2 trans, trans 18.5 C18:3 cis, cis, cis 11.0 C20:3 trans, trans, trans 29.5 **Table 2.** Changes in the melting point of various *cis – trans* geometrical isomers of different fatty acids

In general, all fatty acids naturally present positional isomerism of their more frequent molecular structure. However, these isomers occur in very low concentrations. Unlike the known biochemical and nutritional effects of *trans* geometric isomers, there is little information about the biological effects of positional isomers and for the majority of them these effects are considered as not relevant, except for some conjugated structures, such as conjugated linoleic acid (C18:2, Δ9, Δ11, CLA), a geometric and positional isomer of the most common linoleic acid, for which it has been attributed various health properties, especially those related to anti-inflammatory and lipolytic actions, but up to date the scientific evidence for these properties are considered insufficient [47]. Such as geometrical isomerism, the technological manipulation of fatty acids (i.e. temperature and/or hydrogenation) increases the number and complexity of the positional isomers [48]. Figure 5

Phospholipids are minor components in our diet because less than 4-5% of our fat intake corresponds to phospholipids. However, this does not detract nutritionally important to these lipids, since they are important constituents of the cellular structure having also relevant metabolic functions [49]. Life, in its origin, would not have been possible without the appearance of phospholipids, as these structures are the fundamental components of all cellular membranes. Phospholipids have structural and functional properties that distinguish them from their counterparts, triacylglycerides. In phospholipids positions sn-1 and sn-2 of the glycerol moiety are occupied by fatty acids, more frequently polyunsaturated fatty acids, linked to glycerol by ester bonds. The sn-3 position of glycerol is linked to orthophosphoric acid [50]. The structure which is formed, independent of the type of fatty acid that binds at sn-1 and sn-2, is called phosphatidic acid. The presence of phosphate substituent at the sn-3 position of the glycerol gives a great polarity to this part of the molecule, being non-polar the rest of the structure, such as in triacylglycerides. This

summarizes the positional and geometric isomers of unsaturated fatty acids.

**7. Phospholipids** 

**Figure 4.** Geometric isomerism of fatty acids

#### **6.2. Positional isomers of fatty acids**

Positional isomerism refers to the different positions that can occupy one or more double bonds in the structure of a fatty acid. For example, oleic acid (C18:1 Δ9c), is a common fatty acid in vegetable oils, particularly in olive oil, but vaccenic acid (C18:1 Δ11t) is more common in animal fats. This is a double example, since both fatty acids are geometric


isomers (oleic acid *cis* and vaccenic acid *trans*) and at the same time positional isomers, since oleic acid has a double bond at the Δ9 position and vaccenic acid at the Δ11 position [46].

**Table 2.** Changes in the melting point of various *cis – trans* geometrical isomers of different fatty acids

In general, all fatty acids naturally present positional isomerism of their more frequent molecular structure. However, these isomers occur in very low concentrations. Unlike the known biochemical and nutritional effects of *trans* geometric isomers, there is little information about the biological effects of positional isomers and for the majority of them these effects are considered as not relevant, except for some conjugated structures, such as conjugated linoleic acid (C18:2, Δ9, Δ11, CLA), a geometric and positional isomer of the most common linoleic acid, for which it has been attributed various health properties, especially those related to anti-inflammatory and lipolytic actions, but up to date the scientific evidence for these properties are considered insufficient [47]. Such as geometrical isomerism, the technological manipulation of fatty acids (i.e. temperature and/or hydrogenation) increases the number and complexity of the positional isomers [48]. Figure 5 summarizes the positional and geometric isomers of unsaturated fatty acids.
