STRUCTURE AND PROPERTIES OF BIOMOLECULES - A. E. Zemlyakov - 2017

15. LIPIDS: CLASSIFICATION AND STRUCTURE

Lipids are low-molecular-weight Organic compounds extracted from Cells using non-polar Solvents. Their primary biological function is Participation in the formation of Introduction/36.html">Biological Membranes.

Lipids are structurally very diverse, encompassing derivatives of higher acids, alcohols, aldehydes, and Steroids. The Structure of most lipids features hydrophilic, polar groups on one side and hydrophobic (lipophilic), non-polar radicals on the other. In A number of structures, the polar and non-polar parts are linked via a bridging unit.

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Such amphiphilic molecules—meaning they possess a dual affinity—readily aggregate in an aqueous environment.

❖ Classification of Lipids. There are two main groups of lipids:

✵ Simple (neutral) lipids. These include, in particular:

♦ triglycerides, which are esters of glycerol and higher carboxylic acids;

♦ Waxes;

♦ sterols.

✵ Complex (polar) lipids, which are subdivided into:

♦ Phospholipids, whose polar moiety contains phosphoric acid and its derivatives;

♦ sulfolipids, whose polar moiety contains sulfuric acid residues, typically incorporated into a carbohydrate fragment;

♦ Glycolipids, in which mono- and Oligosaccharides act as the polar HEAD groups.

Based on The Nature of the bridging unit, lipids are divided into two groups.

♦ Glycerolipids, whose structural backbone is the polyhydric alcohol glycerol.

While glycerol itself is optically inactive, the introduction of any substituent at a primary hydroxyl group renders the central carbon atom asymmetric. The positions of substituents in the glycerol molecule are designated using the stereospecific numbering (sn) system. According to this system, if the hydroxyl at C2 is on the left in a Fischer projection, the top carbon is assigned the number 1.

♦ Sphingolipids, which are built upon a lipophilic amino alcohol, such as sphingosine.

Simple Lipids

❖ Triglycerides — esters of glycerol and higher carboxylic acids. They are present in minor amounts in PLANT AND ANIMAL Cell membranes. They serve as the primary component of natural oils and fats, fulfilling an energy-storage function in the Organism. The hydroxyl groups of glycerol are typically acylated with various carboxylic acids. A high content of unsaturated acids in plant triglycerides gives them a liquid state of aggregation (oils), whereas saturated acids lead to a solid consistency in animal-derived triglycerides (fats).

❖ Fatty acids. Components of all three lipid groups include higher carboxylic acids of A wide variety of structures. More than 500 fatty acids have been discovered in nature. The structures of the main Fatty acids are presented below in Table 10. Carboxylic acids with a relatively small number of carbon atoms (C₄-C10) are found among milk lipids. Decanoic and lauric acids are found in fairly large quantities in palm oil lipids. The most common acids in nature contain from 16 to 22 carbon atoms. Fatty acids with more than 30 carbon atoms are significantly rarer, with their primary sources being waxes and bacterial lipids.

Table 11. Structure and names of major naturally occurring carboxylic acids

Saturated acids with an even number of carbon atoms and unsaturated carboxylic acids with one or more cis-double bonds are the most common. In polyenoic acids, the double bonds are typically separated by a methylene group. Acids containing a triple bond, a cyclic structure (cyclohexane and cyclopropane fragments are found in bacterial lipid acids, such as TDM), or a hydroxyl group—for instance, 3-hydroxytetradecanoic (3-hydroxymyristic) acid as a component of lipid A—are significantly less common in biological systems.

Higher acids and acid residues are designated using a shorthand notation in which the first digit indicates the total number of carbon atoms and the second indicates the number of multiple bonds. Letters and numbers denote THE POSITION OF multiple bonds: the number specifies the carbon atom index, while the letters indicate the type and configuration of the multiple bond (a for a triple bond, c for cis-configuration, t for trans-configuration). For example, octadec-6-ynoic (tariric) acid is denoted as 18:1 6a. These conventional Abbreviations are also used when recording lipid structures.

Linoleic (18:2 9c12c) and linolenic (18:3 9c12c15c) acids are Essential Fatty Acids because they are not synthesized in The Human Body and must be obtained exclusively from diet. Arachidonic acid (20:4 5с8с11с14с) is also of vital importance, as it is required for The Biosynthesis of biologically active compounds such as Prostaglandins, thromboxanes, and Leukotrienes. A mixture of these acids is referred to as vitamin F.

For polyenoic acids in which the double bonds are separated by a methylene group, an alternative designation is used: the letter ω is followed by the carbon atom number of the first double bond counted from the methyl end of the molecule. For example, linolenic acid is denoted as 18:3 ω3, and arachidonic acid as 20:4 ω6.

❖ FATTY ACID BIOSYNTHESIS. The synthesis of palmitic acid in animal cells occurs within a multienzyme complex known as fatty acid synthase, which is a dimer of identical 240 kDa subunits. The N-terminal region of the protein contains three catalytic domains: 3-ketoacyl synthase (KS), malonyl/acetyltransferase (MAT), and 3-hydroxyacyl dehydratase (DH). In turn, the C-terminal region features three enzymatically active sites: enoyl reductase (ER), 3-ketoacyl reductase (KR), thioesterase (TE), and the acyl carrier protein (ACP). A large core fragment (up to 600 amino acid residues) is located between these active sites. The acyl carrier protein contains a 4-phosphopantetheine prosthetic group whose thiol group can be acylated, thereby facilitating the sequential transfer of the carboxylic acid residue from one enzyme to another.

Synthesis begins with The transfer of an acetyl group from an acetyl-CoA molecule to the ACP, catalyzed by malonyl/acetyltransferase. Next, the acetyl fragment is transferred to the thiol group of the Cysteine residue in the KS domain, while the thiol group of the ACP is acylated with malonyl-CoA.

The interaction between acetyl-KS and malonyl-ACP results in the transfer of two carbon atoms from the first molecule to the second, accompanied by the release of carbon dioxide. In acetoacetyl-ACP, the keto group is successively reduced, the hydroxyl group is eliminated, and the double bond is reduced. The transformation cycle culminates in butyryl-KS—meaning that the initial carbon chain of acetyl-KS has been extended by two carbon atoms.

A new cycle begins with the interaction of butyryl-KS and malonyl-ACP, and ends with The formation of the caproic acid KS-derivative. The final stage involves The production of palmitoyl-ACP, which is cleaved by the action of a hydrolytic thioesterase to release palmitic acid.

Thus, the end product of biosynthesis in animal cells is palmitic acid. Subsequent biochemical transformations yield saturated and unsaturated acids with a greater or lesser number of carbon atoms.

In plant cells, shorter carboxylic acids can be released from the enzyme complex. The even number of carbon atoms in these acids is due to the successive addition of two-carbon units derived from malonyl-CoA.

❖ Trans-unsaturated acids. In recent years, The impact of trans-Unsaturated fatty acids on the human body has been widely debated in society. Margarine is the primary source of these acids, typically accounting for 5–10% of its total fatty acid content, and reaching up to 50% in some samples. Trans-unsaturated acids are formed during the hydrogenation of cis-unsaturated carboxylic acid residues in vegetable oils. Alongside reduction processes, catalyst surfaces also promote the isomerization of double bonds.

The structures of several trans-acids found in margarines are shown below, with 9-cis, 11-trans-octadeca-9,11-dienoic acid being the principal one.

❖ Waxes. This group encompasses lipids produced by animals and plants, which are esters of higher carboxylic acids and higher alcohols or sterols. Waxes typically consist of mixtures of these esters, higher carboxylic acids, and alcohols.

Typical representatives of animal-derived waxes include:

♦ beeswax (with myricyl palmitate as the main component),

♦ spermaceti from sperm whales (based on cetyl palmitate),

♦ lanolin—sheep wool wax, based on cholesteryl palmitate).

Examples of plant waxes include palm wax and carnauba wax, derived from the wax palm and Brazilian wax palm, respectively. The primary components of these waxes are esters of myricyl alcohol (C₃₀H₆₁OH) with cerotic acid (C₂₅H₅₁COOH) and lignoceric acid (C₂₃H₄₇COOH), respectively.

❖ Sterols — unsaponifiable lipids based on a cyclopenta[a]phenanthrene (estrane) ring system. They are classified into the following groups:

♦ phytosterols, encompassing over 200 compounds, notably β-sitosterol (the major sterol of higher plants), as well as stigmasterol (found in soybean oil) and brassicasterol (found in rapeseed oil);

♦ mycosterols, such as ergosterol, which is found in Fungi and Yeasts and serves as a precursor for the synthetic production of vitamin D;

♦ zoosterols, such as Cholesterol, which is widely distributed in animal cells. Cell membranes contain 7-15% sterol. Even higher concentrations (up to 25%) are found in the myelin sheath of Nerve Cells and in Erythrocyte membranes. The presence of cholesterol significantly affects the fluidity and permeability of lipid bilayers. It serves as a precursor in the biosynthesis of Steroid Hormones and vitamin D. Approximately 80% of human cholesterol is synthesized endogenously, while only about 20% is obtained from the diet. Alongside sterols, cholesterol esters are also widespread in nature.

Complex Lipids

❖ Phospholipids (PLs) — the major components of lipid membranes. Chemically, they are esters of phosphoric acid with two alcohols: glycerol and sphingosine.

✵ Glycerophospholipids (GPLs).

♦ Based on the nature of their hydrophobic tails, they are subdivided into:

a) diacyl GPLs;

b) alkylacyl GPLs — containing a higher alcohol residue; these are rare lipids, most commonly found in Mollusks;

c) plasmalogens — vinyl ethers that yield higher aldehydes upon Hydrolysis; they are found in virtually all organisms.

♦ Based on the Nature of the substituent attached to the phosphoric acid residue, a distinction is made between:

(I) phosphatidylcholine (lecithin), found in the Tissues of Higher Plants and animals (up to 50% of total PLs);

(II) phosphatidylethanolamine (cephalin) — the second most abundant PL, also prevalent in bacterial cells (15-30%);

(III) phosphatidylserine — particularly abundant in the Brain (up to 15% of total lipids), Heart, Kidneys, and Spleen (~10%);

(IV) phosphatidylglycerol — the primary PL of Bacteria (up to 70%), also abundant in plant cells (20-30%);

(V) phosphatidylinositol — contains the cyclic polyol myo-Inositol as its polar head group. It is found in virtually all animal tissues (up to 10% of total PLs), as well as in plants and microorganisms; notably, it is a structural component of lipoarabinomannan in mycobacterial cell walls.

✵ Sphingophospholipids are located in animal tissues, predominantly in the membranes of brain cells and neural tissue, as well as in erythrocyte membranes (30-40% of total lipids). The most widely represented are the phosphoesters of N-acylsphingosines (ceramides). Their acyl components typically include saturated and monounsaturated fatty acids: stearic, lignoceric (24:0), and nervonic (24:1 15c) acids.

Ceramides are not only components of Biomembranes, but also play a vital role as signaling molecules in the Cell life cycle, including Cell Differentiation, inhibition of cell proliferation, and stimulation of apoptosis—programmed cell death.

❖ Glycolipids. Mono- or oligosaccharides act as the polar moiety in this group of lipids. The carbohydrate component is linked to the lipid moiety via an O-glycosidic or ester bond. Lipid A represents another type of glycolipid.

✵ Glyceroglycolipids are the major Lipid Components of METABOLISM/14.html">Chloroplasts. In these glycolipids, the primary hydroxyl group of diacylglycerol is typically glycosylated with glucose or galactose.

✵ Sulfoglycolipids are quite widespread in plant cells. A typical representative of this group of glycolipids is sulfoquinovosyldiacylglycerol.

✵ Trehalose dimycolate (TDM) is a bacterial glycolipid that is a diester of the non-reducing disaccharide trehalose and mycolic acids.

Mycolic acids are higher α-branched β-hydroxy acids with a carbon chain length ranging from ~30 to over 100 carbon atoms (some of the mycolic acid structures are shown in the figure). TDM exhibits immunostimulating and antitumor properties, but its medical application is hindered by high toxicity.

✵ Glycosylceramides are Glycosides of N-acylsphingosine (ceramide). They are found in the brain, spleen, kidneys, and Liver. The carbohydrate moiety is represented by glucose, galactose, N-acetylglucosamine, and N-acetylgalactosamine. The following groups are distinguished:

♦ cerebrosides, where the carbohydrate moiety is a monosaccharide (usually galactose, less frequently glucose), for example, nervon;

♦ globosides, in which ceramides are glycosylated with oligosaccharides;

♦ gangliosides, which contain sialic acids, such as N-acetylneuraminic acid (NeuNAc), along with a tetrasaccharide block. Gangliosides are particularly abundant in the grey matter of the brain. They are predominantly located On the surface of phospholipid membranes and are involved in cell growth, intercellular adhesion, reception, and other processes.

Gangliosides are designated by the letter G, with letter subscripts indicating the number of neuraminic acid residues (M for one, D for two, T for three), while other numbers and letters in the subscript encode the arrangement of these acids.