**7. Phospholipids**

10 Lipid Metabolism

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

**6.2. Positional isomers of fatty acids** 

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].

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 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

#### 12 Lipid Metabolism

double feature, a polar extreme and a non-polar domain due the presence of the two fatty acids characterizes phospholipids as amphipathic molecules (*amphi*: both; *pathos*: sensation) [51].

Overview About Lipid Structure 13

**Figure 6.** Chemical structure of phosphatidic acid and its simplified representation

inflammatory effects, and is a mediator of anaphylactic reactions [55].

These more complex phospholipids are much more common than phosphatidic acid, since this is only the structural precursor of the above molecules. Figure 7 shows the structure of various phospholipids. A number of other molecules are also classified as phospholipids, but are structurally different. Cardiolipin is a "double" phospholipid in which two phosphatidic acid molecules are attached through their phosphates by a molecule of glycerol. Cardiolipin is a very important in the structure of the inner membrane of mitochondria and due their molecular volume it is the only immunogenic phospholipid (which stimulates the formation of antibodies) [53]. Plasmalogens are other lipid molecules related to phospholipids. In these molecules the substituent at sn-1 position of the glycerol is not a fatty acid, but a fatty alcohol which is linked to glycerol by an ether linkage. Phosphatidalethanolamine (different than phosphatidylethanolamine) is an abundant plasmalogen in the nervous tissue [54]. Phosphatidalcholine, the plasmalogen related to phosphatidylcholine, is abundant in the heart muscle. Another structures related to phospholipids are sphingolipids. In these structures glycerol is replaced by the amino alcohol; sphingosine. When the hydroxyl group (alcoholic group) of sphingosine is substituted by phosphocholine, it is formed sphingomyelin, which is the only sphingolipid that is present in significant amount in human tissues as a constituent of myelin that forms nerve fibers [ref]. Platelet activating factor (PAF) is an unusual glycerophospholipid structure. In this molecule position sn-1 of glycerol is linked to a saturated alcohol through an ether bond (such as in plasmalogens) and at the sn-2 binds an acetyl group instead of a fatty acid. PAF is released by a variety of cells and by binding to membrane receptors produces aggregation and degranulation of platelets, has potent thrombotic and

**Figure 5.** Positional and geometric isomers of unsaturated fatty acids

The structure of phospholipids is usually simplified representing the polar end as a sphere and the fatty acids as two parallel rods. Figure 6 shows the chemical structure of phosphatidic acid in its simplified representation. The amphipathic character of phosphatidic acid can be increased by joining to the phosphate different basic and polar molecules that increases the polarity to the extreme of the sn-3 position. When the substituent of the phosphate group is the aminoacid serine it is formed phosphatidylserine; when it is etanolamine it is formed phosphatidylethanolamine (frequently known as cephalin); when choline is the substituent it is formed phosphatidylcholine (well known as lecithin); and when the substituent is the polyalcohol inositol it is formed phosphatidylinositol, a very important molecule involved in cell signaling. [52].

**Figure 6.** Chemical structure of phosphatidic acid and its simplified representation

12 Lipid Metabolism

[51].

double feature, a polar extreme and a non-polar domain due the presence of the two fatty acids characterizes phospholipids as amphipathic molecules (*amphi*: both; *pathos*: sensation)

**Figure 5.** Positional and geometric isomers of unsaturated fatty acids

The structure of phospholipids is usually simplified representing the polar end as a sphere and the fatty acids as two parallel rods. Figure 6 shows the chemical structure of phosphatidic acid in its simplified representation. The amphipathic character of phosphatidic acid can be increased by joining to the phosphate different basic and polar molecules that increases the polarity to the extreme of the sn-3 position. When the substituent of the phosphate group is the aminoacid serine it is formed phosphatidylserine; when it is etanolamine it is formed phosphatidylethanolamine (frequently known as cephalin); when choline is the substituent it is formed phosphatidylcholine (well known as lecithin); and when the substituent is the polyalcohol inositol it is formed

phosphatidylinositol, a very important molecule involved in cell signaling. [52].

These more complex phospholipids are much more common than phosphatidic acid, since this is only the structural precursor of the above molecules. Figure 7 shows the structure of various phospholipids. A number of other molecules are also classified as phospholipids, but are structurally different. Cardiolipin is a "double" phospholipid in which two phosphatidic acid molecules are attached through their phosphates by a molecule of glycerol. Cardiolipin is a very important in the structure of the inner membrane of mitochondria and due their molecular volume it is the only immunogenic phospholipid (which stimulates the formation of antibodies) [53]. Plasmalogens are other lipid molecules related to phospholipids. In these molecules the substituent at sn-1 position of the glycerol is not a fatty acid, but a fatty alcohol which is linked to glycerol by an ether linkage. Phosphatidalethanolamine (different than phosphatidylethanolamine) is an abundant plasmalogen in the nervous tissue [54]. Phosphatidalcholine, the plasmalogen related to phosphatidylcholine, is abundant in the heart muscle. Another structures related to phospholipids are sphingolipids. In these structures glycerol is replaced by the amino alcohol; sphingosine. When the hydroxyl group (alcoholic group) of sphingosine is substituted by phosphocholine, it is formed sphingomyelin, which is the only sphingolipid that is present in significant amount in human tissues as a constituent of myelin that forms nerve fibers [ref]. Platelet activating factor (PAF) is an unusual glycerophospholipid structure. In this molecule position sn-1 of glycerol is linked to a saturated alcohol through an ether bond (such as in plasmalogens) and at the sn-2 binds an acetyl group instead of a fatty acid. PAF is released by a variety of cells and by binding to membrane receptors produces aggregation and degranulation of platelets, has potent thrombotic and inflammatory effects, and is a mediator of anaphylactic reactions [55].

Overview About Lipid Structure 15

aromatic rings identified as A, B, C and D rings. All sterols have at carbon 3 of A ring a polar hydroxyl group being the rest of the structure non-polar, which gives them certain amphipathic character, such as phospholipids. Sterols have also a double bound at carbons 5 and 6 of ring B [58]. This double bond can be saturated (reduced) which leads to the formation of stanols, which together with plant sterols derivatives are currently used as hypocholesterolemic agents when incorporated into some functional foods. At carbon 17 (ring D) both sterols as stanols have attached an aliphatic group, consisting in a linear structure of 8, 9 or 10 carbon atoms, depending on whether the sterol is from animal origin (8 carbon atoms) or from vegetable origin (9 or 10 carbon atoms) [59]. Figure 9 shows the structure of cyclopentanoperhydrophenanthrene and cholesterol. Often sterols, and less frequent stanols, have esterified the hydroxyl group of carbon 3 (ring A) with a saturated fatty acid (usually palmitic; C16:0) or unsaturated fatty acid (most frequent oleic; C18:1 and less frequent linoleic acid; C18:2. The esterification of the hydroxyl group eliminates the anphipaticity of the molecule and converts it into a structure completely non-polar. Undoubtedly among sterols cholesterol is the most important because it is the precursor of important animal metabolic molecules, such as steroid hormones, bile salts, vitamin D, and oxysterols, which are oxidized derivatives of cholesterol formed by the thermal manipulation of cholesterol and that have been identified as regulators of the metabolism and homeostasis of cholesterol and sterols in

**Figure 8.** Simulation how the structural differences of the fatty acids which comprise phospholipids

may affect the physical and chemical behavior of a membrane

general [60].

**Figure 7.** Structure of various phospholipids

A fundamental aspect of phospholipids is their participation in the structure of biological membranes, and the structural characteristics of the fatty acids are relevant to determine the behavior and the biological properties of the membrane. As an example, a diet rich in saturated fatty acids result in an increase in the levels of these fatty acids into cell membrane phospholipids, causing a significant decrease in both, membrane fluidity and in the ability of these structure to incorporate ion channels, receptors, enzymes, structural proteins, etc., effect which is associated to an increased cardiovascular risk [56]. By contrast, a diet rich in monounsaturated and/or polyunsaturated fatty acids produce an inverse effect. At the nutritional and metabolic level this effect is highly relevant because as the fatty acid composition of the diet is directly reflected into the fatty acid composition of phospholipids, changes in the composition of the diet, i.e. increasing the content of polyunsaturated fatty acids, will prevent the development of several diseases [57]. Figure 8 shows a simulation how the structural differences of the fatty acids which comprise phospholipids may affect the physical and chemical behavior of a membrane.

#### **8. Sterols**

Sterols are derived from a common structural precursor, the sterane or cyclopentanoperhydrophenanthrene, consisting in a main structure formed by four aromatic rings identified as A, B, C and D rings. All sterols have at carbon 3 of A ring a polar hydroxyl group being the rest of the structure non-polar, which gives them certain amphipathic character, such as phospholipids. Sterols have also a double bound at carbons 5 and 6 of ring B [58]. This double bond can be saturated (reduced) which leads to the formation of stanols, which together with plant sterols derivatives are currently used as hypocholesterolemic agents when incorporated into some functional foods. At carbon 17 (ring D) both sterols as stanols have attached an aliphatic group, consisting in a linear structure of 8, 9 or 10 carbon atoms, depending on whether the sterol is from animal origin (8 carbon atoms) or from vegetable origin (9 or 10 carbon atoms) [59]. Figure 9 shows the structure of cyclopentanoperhydrophenanthrene and cholesterol. Often sterols, and less frequent stanols, have esterified the hydroxyl group of carbon 3 (ring A) with a saturated fatty acid (usually palmitic; C16:0) or unsaturated fatty acid (most frequent oleic; C18:1 and less frequent linoleic acid; C18:2. The esterification of the hydroxyl group eliminates the anphipaticity of the molecule and converts it into a structure completely non-polar. Undoubtedly among sterols cholesterol is the most important because it is the precursor of important animal metabolic molecules, such as steroid hormones, bile salts, vitamin D, and oxysterols, which are oxidized derivatives of cholesterol formed by the thermal manipulation of cholesterol and that have been identified as regulators of the metabolism and homeostasis of cholesterol and sterols in general [60].

14 Lipid Metabolism

**Figure 7.** Structure of various phospholipids

of a membrane.

**8. Sterols** 

A fundamental aspect of phospholipids is their participation in the structure of biological membranes, and the structural characteristics of the fatty acids are relevant to determine the behavior and the biological properties of the membrane. As an example, a diet rich in saturated fatty acids result in an increase in the levels of these fatty acids into cell membrane phospholipids, causing a significant decrease in both, membrane fluidity and in the ability of these structure to incorporate ion channels, receptors, enzymes, structural proteins, etc., effect which is associated to an increased cardiovascular risk [56]. By contrast, a diet rich in monounsaturated and/or polyunsaturated fatty acids produce an inverse effect. At the nutritional and metabolic level this effect is highly relevant because as the fatty acid composition of the diet is directly reflected into the fatty acid composition of phospholipids, changes in the composition of the diet, i.e. increasing the content of polyunsaturated fatty acids, will prevent the development of several diseases [57]. Figure 8 shows a simulation how the structural differences of the fatty acids which comprise phospholipids may affect the physical and chemical behavior

Sterols are derived from a common structural precursor, the sterane or cyclopentanoperhydrophenanthrene, consisting in a main structure formed by four

**Figure 8.** Simulation how the structural differences of the fatty acids which comprise phospholipids may affect the physical and chemical behavior of a membrane

Overview About Lipid Structure 17

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**Figure 9.** Structure of cyclopentanoperhydrophenanthrene and cholesterol
