Fundamentals of Biochemistry - Filippovich, Y. B. 1999

Lipids and Their Metabolism
Simple Lipids

Fats. Fats are exceptionally widespread in nature: they are found in the bodies of humans, animals, plants, microorganisms, and even certain Viruses. In some biological objects, tissues, and Organs, their content reaches 90%.

The term "fat" is used in two ways. Substances referred to as fats in everyday life (beef fat, butter, etc.) are not chemically defined compounds, as they consist of multiple components: mixtures of various triglycerides, free Higher Fatty acids, pigments, Aromatic Compounds, and frequently cellular structures. In this sense, therefore, fat is a more morphological or technological concept. Specifically, plant fats are conventionally called oils, and morphologically distinct animal fats are referred to as lard or tallow. Over 600 Different types of fats have been isolated from various sources, including 420 types of plant origin, 80 types from land animals, and more than 100 types from aquatic organisms.

From a compositional standpoint, fats are defined as strictly specific compounds, namely, esters of higher Fatty Acids and the trihydric alcohol glycerol.

Consequently, chemists prefer to use the term triglycerides (for triglyceride formulas, see below).

More than five hundred organic acids have been identified in natural triglycerides, and this list expands every year. A major proportion of these consists of higher fatty monocarboxylic acids, i.e., acids with a molecular carbon chain length of 16 or more atoms. Higher organic acids found in triglycerides frequently contain double bonds and hydroxyl groups in their hydrocarbon radical. Table 25 presents a list, formulas, and melting points of the acids most commonly found in fats.

Class="center">Table 25 Some monocarboxylic acids isolated from natural fats

As can be seen from the table data, natural fats initially were found to contain almost exclusively straight-chain acids with an even number of carbon atoms in the molecule. Only isovaleric acid, discovered in dolphin Liver fat, had an odd number of carbon atoms and a branched chain.

Recently, new highly efficient Methods for Separation (thin-layer and gas Chromatography) and structural determination (infrared spectrophotometry) of higher fatty acids have been developed. As a result, A number of new higher fatty acids have been discovered in natural fats, including cyclic ones, those with an odd number of carbon atoms, and those with a branched carbon Skeleton. The latter, in particular, significantly lower the melting point of fats, exhibit antibiotic properties, and display species Specificity. One such representative is, for example, mycolic acid isolated from tubercle bacilli:

Oleic acid is encountered most frequently and in the largest proportion in natural fats (comprising over 30% of most fats), alongside palmitic acid (ranging from 15 to 50% in most cases). Therefore, oleic and palmitic acids are classified as the principal fatty acids contained in fats. The remaining Fatty acids are generally present in natural fats in small amounts (a few percent), and only in certain types of natural fats does their content reach tens of percent. Thus, butyric and caproic acids are well represented in certain animal-derived fats, while caprylic and capric acids are abundant in coconut oil. Lauric acid is prevalent in laurel oil, myristic acid in nutmeg oil, and arachidic, behenic, and lignoceric acids in peanut and soybean oils. Polyunsaturated higher fatty acids—linoleic and linolenic—constitute the major fraction of linseed, hemp, sunflower, cottonseed, and certain other vegetable oils. Stearic acid is present in significant quantities (25% or more) in some hard animal fats (mutton and beef tallow) and tropical plant oils (coconut oil).

Animal and plant fats exhibit certain distinguishing features. Animal fats are more diverse in their composition of higher fatty acids. In particular, higher fatty acids with 20 to 24 carbon atoms are more frequently encountered among them. In plant fats, the proportion of unsaturated higher fatty acids is very high (up to 90%), and among saturated acids, only palmitic acid is present in amounts of 10–15%.

Triglycerides are divided into simple and mixed. The former are esters of glycerol and a single higher acid, for example:

The latter are built from a glycerol residue and residues of different higher fatty acids:

In natural fats, which are mixtures of diverse triglycerides, the proportion of simple triglycerides is negligible, whereas the percentage of mixed triglycerides can be very high. For instance, out of 8 different triglycerides found in lard, only 1% is tripalmitin and 3% is triolein. The remaining six triglycerides of pork fat are mixed, with palmitodioleine (53%) and palmitostearoolein (27%) predominating. Stearodipalmitin, oleodipalmitin, myristodipalmitin, myristodilaurin, palmitodimyristin, and laurodimyristin have been found in coconut and palm oils. Thus, natural fats extracted from a given source always represent complex mixtures of various triglycerides mutually dissolved in one another.

Fig. 121. Structure and molecular shape of a triglyceride

The Physical Properties of triglycerides depend on The Nature of the higher fatty acids incorporated into their molecules. This relationship becomes particularly evident when examining the melting points of triglycerides: if saturated (solid) fatty acids predominate in the triglyceride, the triglyceride is also solid; if unsaturated (liquid) acids predominate, the melting point of the triglyceride is low, and it remains liquid under ordinary conditions.

The same relationship is observed in natural fats: the presence predominantly of saturated triglycerides results in a high melting point, whereas unsaturated ones result in a low melting point. Mutton tallow, for instance, has a melting point approximately 10 °C higher than that of lard because it contains a few percent less palmitodioleine (46% and 53%, respectively) and more oleodipalmitin (13% and 5%, respectively). The low melting point of many vegetable oils is in complete agreement with the substantial content of unsaturated acids within their triglycerides. For example, the triglycerides of sunflower oil, which is liquid under normal conditions (t_m = -21 °С), contain 39% oleic and 46% linoleic acid, whereas the hard vegetable fat from cocoa beans (t_m = 30–34 °С) consists of 35% palmitic and 40% stearic acids.

Triglycerides form optical and geometrical isomers because they frequently possess an asymmetric carbon atom in the glycerol moiety and one or more double bonds in the acid radical chains. Numerous combinations arising from the rearrangement of acyl groups in mixed triglycerides give rise to families of structural isomers. Characteristically, unsaturated higher fatty acids in triglycerides generally adopt the cis-configuration, which affects the molecular shape (Fig. 121).

Thus, a vast number of individual triglycerides can potentially exist in nature, ensuring their species and other specificities. However, the actual state of affairs remains unknown: The problem of spatial isomerism and species specificity of fats has been scarcely studied.

Waxes. Waxes are a group of simple Lipids that are esters of higher alcohols and higher monocarboxylic acids. In addition to these esters, natural waxes contain certain amounts of free higher alcohols and higher acids, as well as minor amounts of Hydrocarbons—invariably with an odd number of carbon atoms (ranging from 27 to 33)—along with coloring and aromatic substances. The total amount of these impurities can reach 50%. Waxes are found in both the animal and plant kingdoms, where they primarily perform protective Functions. In plants, for instance, they coat leaves, stems, and fruits in a thin layer, protecting them against wetting by Water and the penetration of microorganisms. The storage life of fruits depends, among other things, on the quality of the wax coating. Honey is stored and bee larvae develop under a layer of beeswax. Other Types of Animal wax (lanolin) protect Hair and Skin from the action of water. All waxes are solid substances of various colors—most commonly yellow or greenish (depending on their origin); their melting points range from 30 to 90 °C. Several dozen higher fatty acids and alcohols have been identified in waxes, both in the free state and as esters. Some of these include:

Alcohols and acids containing 32 and 34 carbon atoms in their molecules have been found in beeswax and the wax coating The surface of plant leaves and fruits. One type of Japanese wax contains higher dicarboxylic acids. Higher unsaturated alcohols, such as oleyl alcohol, have been detected in fish and whale fats. Unsaturated acids are relatively rare in waxes.

Spermaceti is an animal-derived wax obtained from the spermaceti oil of the sperm whale's cranial cavities through freezing and pressing. It consists primarily (about 90%) of palmityl palmitate (cetyl palmitate): СН₃—(СН₂)₁₄—СО—О—СН₂—(СН₂)₁₄—СН₃. Spermaceti is a solid substance with a melting point of t_пл=41— 49° С.

The fraction remaining after the extraction of spermaceti from sperm whale oil represents liquid wax. It consists of a mixture of liquid oleyl oleate: СН₃—(СН₂)₇—СН=СН—(СН₂)₇—СО—О—СН₂—(СН₂)₇—СН=СН—(СН₂)₇—СН₃ along with other liquid esters whose components are either oleic acid or oleyl alcohol.

Myricyl palmitate predominates in beeswax: СН₃—(СН₂)₁₄—СО—О—СН₂—(СН₂)₂₈—СН₃. It is also characterized by a high content of free higher fatty acids (up to 13.5%) and hydrocarbons (up to 12.5%). The melting point of beeswax is 62—70° С.

The wax of the palm tree Copernicia cerifera, which grows in Brazil and is known as carnauba wax, is essentially ceryl myricate: СН₃—(СН₂)₂₄—СО—О—СН₂—(СН₂)₂₈—СН₃. Carnauba wax is a yellowish-gray substance that coats the palm leaves, protecting the plant from moisture loss.

Montan wax can be extracted from brown coal or peat using organic Solvents; it consists of montanic acid and its esters (t_пл = 72 — 74° С).

Waxes are more resistant to light, oxidizing agents, heat, and other physical factors, and undergo Hydrolysis less readily than fats. There are known cases where beeswax has been preserved for millennia. This is precisely why waxes perform protective functions in living organisms.

Sterides. A large group of simple lipids consists of sterides, which are esters of specifically structured cyclic alcohols (sterols) and higher fatty acids. Sterides form the saponifiable fraction of lipids.

In nature, the fraction of unsaponifiable, free sterols and related compounds is much more widely represented than sterides. For instance, in The Human Body, only 10% of sterols are esterified and exist as sterides, while 90% are free and form the unsaponifiable fraction. The ratio of sterols to sterides varies across different tissues and Body Fluids: the liver contains them in equal amounts, whereas Bile contains exclusively free sterols.

Sterols have a rather complex structure. Their molecules are based on a cyclic system of atoms consisting of reduced phenanthrene (fully reduced phenanthrene is called perhydrophenanthrene) and cyclopentane. This cyclic system is termed cyclopentanoperhydrophenanthrene, or sterane. Sterane bearing a carbon side chain and two CH₃ groups (at the 10th and 13th carbon atoms of the cycle) is called cholestane:

Carbon atoms in these hydrocarbons are designated based on the numbering system adopted for phenanthrene (carbon atoms 1–14); the fourth ring is numbered next, and only then does numbering proceed to the carbon atoms in the side chains. Rings are conventionally designated by uppercase letters of the Latin alphabet.

When oxidized at position 3 (ring A), cholestane is converted into a polycyclic alcohol, cholestanol, which gives rise to the class of sterols:

However, one should not assume that sterols are formed in nature through the reduction of phenanthrene. It has been established that their Biosynthesis proceeds via the cyclization of polyisoprenoids, which essentially serve as precursors to sterols (see below).

The characteristic core of cholestanol is repeated in all sterols with minor variations. These variations involve either the appearance of double bonds between carbon atoms 5–6 and 7–8 of ring B, or between carbon atoms 22–23 of the side chain, or the presence of a radical at position 24 (in the side chain) that may have the structure —СН₃; = СН₂; —С₂Н₅; = СН—СН₃, etc. Formulas for the most important natural sterols are given below:    

Cholesterol (from the Greek chole – bile) is the principal sterol in animals and humans, meaning it belongs to zoosterols. Ergosterol is characteristic of Fungi. Sitosterol and stigmasterol are typical plants sterols (phytosterols): the former is found, for example, in soybean oil, and the latter in wheat germ oil. Fucosterol has been detected in brown Algae. The presence of a particular sterol is often specific to a certain class or family of animals or plants. For instance, Sponges contain a number of unique sterols with 28 and 29 carbon atoms in their molecules, whereas starfish and sea cucumbers contain specific stellasterols. It has been observed that the more primitive the Organism, the more diverse its set of sterols tends to be. Humans possess only one—cholesterol. Currently, over 60 zoosterols and nearly 140 phytosterols are known (A. Kulman, 1989).

Conformational isomers are widespread among sterols. For example, coprostanol is a known isomer of cholestanol, characterized by a different spatial arrangement of its constituent rings:

Upon examining the formulas of cholestanol and coprostanol given above, it is easy to see that rings A and B are in a *trans* configuration relative to each other in the former, and in a *cis* configuration in the latter. Cholestanol is present in animal tissues in small quantities (along with large amounts of cholesterol). Coprostanol is found in animal excrement, as reduced cholesterol is eliminated from the body in the form of coprostanol.

A characteristic feature of natural conformational isomers of sterols is that their OH group at the 3rd carbon atom is located on the same side of the ring as the CH₃ group at the 10th carbon atom. This conformation is designated as ß, while the opposite one is designated as a.

Sterols are crystalline substances that are readily soluble in chloroform, diethyl ether, and hot alcohol, virtually insoluble in water, and resistant to hydrolytic agents. In the animal body, sterols undergo oxidation to yield a whole family of derivatives collectively known as Steroids. These include numerous compounds, of which we shall mention only a few characteristic representatives:

Bile acids are essential components of bile that ensure the normal absorption of fatty acids in the intestines of humans and animals. Estradiol and testosterone are the female and Male Sex Hormones, respectively, which exert a profound influence on vital physiological processes (see Chapter XII).

Esters of zoo- and phytosterols with higher fatty acids form a group of saponifiable substances known as sterides:

Among the higher fatty acids found in sterides, palmitic, stearic, and oleic acids predominate. However, sterides that constitute, for example, the major component of lanolin (the fat fraction of sheep wool) have been found to contain myristic, arachidonic, and cerotic acids, as well as specific branched-chain higher fatty acids such as lanopalmitic, lanostearic, and others.

All sterides, much like sterols, are solid, colorless substances (from the Greek stereos meaning solid). In nature, particularly within animal organisms, they occur as complexes with Proteins, whose functional role is to transport sterols, steroids, and sterides, as well as to participate in The formation of Introduction/36.html">Biological Membranes. An increase in the content of sterols and sterides within the lipid fraction of membranes leads to a decrease in membrane permeability, an increase in viscosity, limited mobility, and the inhibition of several membrane-bound Enzymes. Sterides and sterols also regulate other processes in the body. Certain sterol derivatives are carcinogenic, whereas others (such as testosterone propionate) are used to treat specific types of Cancer. Sterols and sterides are abundant in the Nervous Tissue of humans and animals, where their significance and functions are currently under active investigation.