Lipids
For this chapter, some of the structures are not available in the database that renders the three-dimensional structures, from the Cactus website, a source of JSmol models through the Stolaff College portal. However, these structures will be made available as PNG images that can be rendered by Jmol/JSmol.
Fatty acids and derivatives
Lipids can be presented in two basic types: as hydrocarbons formed by conjugation of ethylenes to carboxylic derivatives of hydrocarbons (derived from acetates), or as steroids, structures of four fused hydrophobic rings and derived from isoprenes. Palmitic acid exemplifies the first type. Every fatty acid is formed by a hydrocarbon “tail” or alkyl chain, and a carboxylic acid “head”. The carbon of the carboxylic group is numbered as C1 or carbon \(\alpha\), and the last carbon of the chain, as carbon \(\omega\). Because they have a pKa value of around 4.8 to 7.7 (proportional to the size of the carbon chain), fatty acids tend to be partially ionized in physiological solution.
Unsaturation and nomenclature of fatty acids
Fatty acids can differ in size (number of carbons) and degree of unsaturation. Palmitic acid represents a fatty acid with saturated bonds, which classifies it as a saturated fatty acid. The insertion of a double bond limits the flexibility of the alkyl chain in this region, and promotes a conformational change that reduces its ability to adhere between molecules. This is an example of oleic acid, an unsaturated fatty acid with 18 carbons (C-18).
The area occupied by an unsaturated fatty acid is also larger, 32 Angstrom\(^{2}\) for oleic acid, while stearic acid, also a C-18, although saturated, has 21 Angstrom\(^{2}\). Each double bond inserted into the structure of a fatty acid alters its local conformation, as exemplified for linolenic acid, with three double bonds in its structure.
Unsaturations also give rise to two configurational isomers, cis and trans, depending on the positioning of the hydrogen atoms, whether opposite in the double bond (trans) or close to and on the same side of it (cis). Thus, cis fatty acids exhibit the hydrogen bond HC=CH in the same direction (linolenic acid, C18, linolenic acid), while trans fatty acids do so in opposite directions. Hence the name trans fat present in industrialized and ultra-processed products, and related to clinical dysfunctions, such as atherosclerosis and cardiac complications.
Because it has the first double bond at the 3rd carbon counted from the last carbon of the chain (carbon \(\omega\)), linolenic acid is also called \(\omega\)-3. This nomenclature allows us to differentiate \(\alpha\)-linolenic acid, an \(\omega\)-3, from \(\gamma\)-linolenic acid, an \(\omega\)-6. And by this nomenclature, oleic acid is considered a fatty acid of the \(\omega\)-9 series.
There are two acids considered essential fatty acids, that is, they require ingestion since they are not produced in mammals, a \(\omega\)-3, linolenic acid, and a \(\omega\)-6, linoleic acid..
A more technical nomenclature, which avoids structural synonyms, is the one that defines the position of each double bond in the structure. Thus, linolenic acid is named 18:3\(^{\Delta~ 9,12,15}\), while linoleic acid displays the code 18:2\(^{\Delta~ 9,12}\).
Chemical reactions of fatty acids
Fatty acids can undergo three main transformations: rancidification, hydrogenation and saponification. rancidification results from the action of molecular oxygen, high temperature and/or microorganisms on unsaturations, promoting cleavage of the fatty acid and release of low molecular weight fatty derivatives, sometimes volatile, and with an unpleasant odor. Hydrogenation* involves an industrial process on unsaturated bonds, making them saturated.
Saponification, in turn, occurs when a strong alkali such as NaOH or KOH interacts with a more complex structure of fatty acids, the triglycerides, triglycerides or, more appropriately, triacylglycerols. These are formed by an ester linkage to each of the three fatty acids to the glycerol alcohol, as exemplified for trimyristin. In short, saponification produces polar amphipathic structures at the end of the carboxylate’s interaction with sodium or potassium ions, which allows its interaction with water, while the nonpolar tails allow interaction with lipid structures, promoting a reduction in the surface tension of the water around the target molecule and, more generally, the cleaning of fats.
Thus, in saponification, the alkaline hydrolysis of the triglyceride releases glycerol and forms a mixture of free fatty acid salts with their ionized carboxylates in interaction with the alkali cation (Na\(^{+}\) or K\(^{+}\)).
Other derivatives
Other structures derived from fatty acids include phospholipids, sphingolipids, and glycolipids. Of these, phospholipids are the most common and are present in the structure of biomembranes, such as lecithin. Lecithin is actually a yellowish lipid compound, formed by mixtures of phosphatidylcholine, phosphatidylserine, phosphatidylethanolamine, acid. phosphatidic acid and phosphatidylinositol, a derivative of inositol. But lecithin can also be considered alone as a molecule of 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine, a phosphatidylcholine. Choline, 2-hydroxyethyl-trimethylammonium, appears as the amino structure linked to the phosphate group.
Sphingolipids, phospholipids commonly found in cell membranes such as the myelin sheath of axons, have a fatty acid-anchoring structure distinct from glycerol, sphingosine (D-erythro-sphingosine). An example is sphingomyelin, usually formed by phosphocholine and ceramide or phosphatidylethanolamine.
Ceramide is also found in the skin of fruits such as apples, in earwax, and in the production of honey. Ceramides inhibit water evaporation in addition to acting physiologically in cellular regulation.
Finally, glycolipids constitute lipids with a covalent bond to a monosaccharide, such as cerebroside, maintain the structural stability of the membrane and facilitate cellular recognition.
Ceramide is also found in the skin of fruits such as apples, in earwax, and in the production of honey. Ceramides inhibit water evaporation in addition to acting physiologically in cellular regulation.
Finally, glycolipids constitute lipids with a covalent bond to a monosaccharide, such as cerebroside, maintain the structural stability of the membrane and facilitate cellular recognition.
Association of fatty acids
Lipids, such as fatty acids, phospholipids or sphingolipids, can undergo self-association in aqueous solvents (blood, for example), leading to the formation of structures such as liposomes, micelles, and biological membranes. Note that in all these associations water maintains its interaction with the polar face of the structure, as exemplified in Figures~\(\ref{micelle2}\) and ~\(\ref{membr}\). In reverse micelles, on the other hand, the opposite occurs when in contact with solvent. The biological membrane, as a lipid bilayer containing phospholipids, also has cholesterol between the aliphatic chains of phospho and sphingolipids, which allows reducing the effect of paracrystallinity with temperature, as well as an extensive set of integral and peripheral proteins, information not available in the structural model.
Vitamin derivatives and inflammatory homeostasis
Fat-soluble vitamins
From aliphatic chains of 20 carbons, several compounds are produced, generating a group called eicosanoids eicoso, from the Greek, twenty). From this group, some vitamins are taken as examples, such as retinol or vitamin A, and tocopherol or vitamin E.
Inflammation mediators
Likewise, inflammation-balancing compounds are also synthesized from lipid precursors, especially arachidonic acid, such as prostaglandins, leukotrienes, and thromboxanes.
Steroids
The second major set of lipids derives from the overlapping linkage of isoprenes, 5C structures that form a steroid molecule called cholesterol. Chemically, cholesterol is an alcohol formed from the fusion of four rings formed by isoprenoids, producing a perhydrocyclophenanthrene ring. When in high levels, cholesterol can form cholesterol crystals due to the hydrophobic effect between its molecules, excluding the aqueous solvent.
Cholesterol derivatives
From cholesterol, several steroid structures are biosynthesized, including sex hormones such as testosterone (or 17-hydroxy-androst-4-en-3-one, a C21), progesterone, and estradiol. Mineralcorticoids are also produced, such as aldosterone (also known as 11,21-dihydroxy-3,20-dioxo-pregn-4-en-18-al, a C21, for blood sodium control), cortisol (chemically, 11,17,21-trihydroxypregn-4-ene-3,20-dione, active in cellular catabolism), fat-soluble vitamins such as vitamin D (calciferol or 7-dehydrocholecalciferol, calcium regulation) and vitamin K (or phylloquinone, warfarin, present in blood clotting), and bile acids (lipid emulsifiers), such as cholic acid, deoxycholic acid, and taurocholic acid, the latter derived from taurine.