Materials preparation to the practical classes

Materials preparation to the practical classes

for the students of pharmaceutical faculty

LESSON № 24

Theme 34. Lipids. Terpenes and terpenoids. Steroids.

Terpenes

         Terpenes  are a large and varied class of hydrocarbons, produced primarily by a wide variety of plants, particularly conifers, though also by some insects such as termites or swallowtail butterflies, which emit terpenes from their osmeterium. They are the major components of resin, and of turpentine produced from resin. The name “terpene” is derived from the word “turpentine”. In addition to their roles as end-products in many organisms, terpenes are major biosynthetic building blocks withiearly every living creature. Steroids, for example, are derivatives of the triterpene squalene. When terpenes are modified chemically, such as by oxidation or rearrangement of the carbon skeleton, the resulting compounds are generally referred to as terpenoids. Some authors will use the term terpene to include all terpenoids. Terpenoids are also known as Isoprenoids. Terpenes and terpenoids are the primary constituents of the essential oils of many types of plants and flowers. Essential oils are used widely as natural flavor additives for food, as fragrances in perfumery, and in traditional and alternative medicines such as aromatherapy. Synthetic variations and derivatives of natural terpenes and terpenoids also greatly expand the variety of aromas used in perfumery and flavors used in food additives. Vitamin A is an example of a terpene. Terpenes are released by trees more actively in warmer weather, acting as a natural form of cloud seeding. The clouds reflect sunlight, allowing the forest to regulate its temperature.

Structure and biosynthesis

Isoprene

Isoprenoides – products of isoprene     transformation. Some vitamins and hormones have isoprenoides structure.

Isoprenoides includes terpens, carotinoids and steroids

Terpenes are derived biosynthetically from units of isoprene, which has the molecular formula C5H8. The basic molecular formulae of terpenes are multiples of that, (C5H8)n whereis the number of linked isoprene units. This is called the isoprene rule or the C5 rule. The isoprene units may be linked together “head to tail” to form linear chains or they may be arranged to form rings. One can consider the isoprene unit as one of nature’s common building blocks.

Isoprene itself does not undergo the building process, but rather activated forms, isopentenyl pyrophosphate (IPP or also isopentenyl diphosphate) and dimethylallyl pyrophosphate (DMAPP or also dimethylallyl diphosphate), are the components in the biosynthetic pathway. IPP is formed from acetyl-CoA via the intermediacy of mevalonic acid in the HMG-CoA reductase pathway. An alternative, totally unrelated biosynthesis pathway of IPP is known in some bacterial groups and the plastids of plants, the so-called MEP(2-Methyl-D-erythritol-4-phosphate)-pathway, which is initiated from C5-sugars. In both pathways, IPP is isomerized to DMAPP by the enzyme isopentenyl pyrophosphate isomerase.

Dimethylallyl pyrophosphate

Isopentenyl pyrophosphate

As chains of isoprene units are built up, the resulting terpenes are classified sequentially by size as hemiterpenes, monoterpenes, sesquiterpenes, diterpenes, sesterterpenes, triterpenes, and tetraterpenes.

Types

 

Second or third instar caterpillar of Papilio glaucus emit terpenes from their osmeterium

Terpenes may be classified by the number of terpene units in the molecule; a prefix in the name indicates the number of terpene units needed to assemble the molecule.

• Hemiterpenes consist of a single isoprene unit. Isoprene itself is considered the only hemiterpene, but oxygen-containing derivatives such as prenol and isovaleric acid are hemiterpenoids.

• Monoterpenes consist of two isoprene units and have the molecular formula C₁₀H₁₆. Examples of monoterpenes are: geraniol, limonene and terpineol.

• Sesquiterpenes consist of three isoprene units and have the molecular formula C₁₅H₂₄. Examples of sesquiterpenes are: farnesenes, farnesol. The sesqui- prefix means one and a half.

• Diterpenes are composed for four isoprene units and have the molecular formula C₂₀H₃₂. They derive from geranylgeranyl pyrophosphate. Examples of diterpenes are cafestol, kahweol, cembrene and taxadiene (precursor of taxol). Diterpenes also form the basis for biologically important compounds such as retinol, retinal, and phytol. They are known to be antimicrobial and antiinflammatory.

• Sesterterpenes, terpenes having 25 carbons and five isoprene units, are rare relative to the other sizes. The sester- prefix means half to three, i.e. two and a half. Examples of sesterterpenes are geranylfarnesol.

• Triterpenes consist of six isoprene units and have the molecular formula C₃₀H₄₈. The linear triterpene squalene, the major constituent of shark liver oil, is derived from the reductive coupling of two molecules of farnesyl pyrophosphate. Squalene is then processed biosynthetically to generate either lanosterol or cycloartenol, the structural precursors to all the steroids.

• Tetraterpenes contain eight isoprene units and have the molecular formula C₄₀H₆₄. Biologically important tetraterpenes include the acyclic lycopene, the monocyclic gamma-carotene, and the bicyclic alpha- and beta-carotenes.

• Polyterpenes consist of long chains of many isoprene units. Natural rubber consists of polyisoprene in which the double bonds are cis. Some plants produce a polyisoprene with trans double bonds, known as gutta-percha.

Terpene biosynthesis

The reaction of dimethylallyl pyrophosphate with isopentenyl pyrophosphate forms geranyl pyrophosphate, a 10-carbon compound. In the first step of the reaction, isopentenyl pyrophosphate acts as a nucleophile and displaces a pyrophosphate group from dimethylallyl pyrophosphate. Pyrophosphate is an excellent leaving group: Its four OH-groups. Therefore, three of the four groups will be primarily in their basic forms at physiological pH A proton is removed in the next step, resulting in the formation of geranyl pyrophosphate.

The higher terpenes are formed not by successive addition of C5 units but by the coupling of simpler terpenes. Thus, the triterpenes (C30) are derived from two molecules of farnesyl pyrophosphate, and the tetraterpenes (C40) from two molecules of geranyl pyrophosphate. These carbon–carbon bond-forming processes involve tail-to-tail couplings and proceed by a more complicated mechanism than that just described. The enzyme-catalyzed reactions that lead to geraniol and farnesol (as their pyrophosphate esters) are mechanistically related to the acid-catalyzed dimerization of alkenes. The reaction of an allylic pyrophosphate or a carbocation with a source of  electrons is a recurring theme in terpene biosynthesis and is invoked to explain the origin of more complicated structural types. Consider, for example, the formation of cyclic monoterpenes. Neryl pyrophosphate, formed by an enzyme-catalyzed isomerization of the E double bond in geranyl pyrophosphate, has the proper geometry to form a six-membered ring via intramolecular attack of the double bond on the allylic pyrophosphate unit.

Monoterpens

They are the terpenes that have been known for several centuries as components of the fragrant oils obtained from leaves, flowers and fruits. Monoterpenes, with sesquiterpenes, are the main constituents of essential oils.

Acyclic monoterpens

They can be considered as derivatives of 2,6-dimethyloctane.

In the basis of carbon skeleton acyclic monoterpens are structures of isoprene isomeric dimers: myrcene and ocimene.

Geraniol and nerol alcohols are derivatives of carbohydrates monoterpens. Geraniol has cis-form and nerol – trance-form.

 

Geraniol and citral present in ether oils, especially in citric oil. They are pheromones.

Monocyclic monoterpenes

They are derived from cyclohexane with an isopropyl substituent. The most important members are limonene and methane.

Limonene (dipentene) can be obtained by isoprene isomerisation with heating to 150 C in soldered ampoule. At 500-700 C reverse processes takes place.

– Catalytically hydrogenisation of limonene

– hydratation of limonene:

Menthane (1-isopropilmethylbenzol) is obtained from p-cimol (n-isopropilmethylbenzol) hydration.

From hydroxyderivatives of menthane most important is menthol (menthanol-3), which has tree asymmetric centers. (-)Menthol synthesized by reducing of menthone.

Menthol has antiseptic, sedative, analgesic properties (Boromenthol, Pectussine).

(+)Menthol in industry synthesized by alkylation of m-crezol with following hydration of tymol.

Terpinehydrate (monohydrate menthandiol-1,8) use in medicine in treatment of chronic bronchitis.

 

Bicyclic monoterpenes:

The same tertiary carbocation serves as the precursor to numerous bicyclic monoterpenes. A carbocation having a bicyclic skeleton is formed by intramolecular attack of the  electrons of the double bond on the positively charged carbon. In the basis of bicyclic monoterpenes are four cyclic terpenic carbohydrates:

α-Pinene contains in turpentine oil – turpentine (up to 75 %).           

Heating with dilute acids (H2SO4, HNO3):

After oxidation on air forms verbenon:

Borneol – alcohol of bornane (camphane) chain:

Isoborneol is borneol’s diastereomer:

Synthesis of difficult esters of borneol.

Oxidation by chromic acid:

Interaction between borneol and acids:

Camphene can hydrolyze in acidic medium with formation of isoborneol.

Camphor – bicyclic ketone, has two asymmetric atoms, but dosen’t have diastereomers.

Camphor uses for stimulation of respiratory and vesselmoving centers, has antiseptic properties, stimulates metabolite processes.

Tishchenko synthesis

Methylene group in α-location (according to carbonyl group) has CH-acidic properties.

Oxidation of camphor with nitrate acid

 

Lipids

Although lipid analysts tend to have a firm understanding of what is meant by the term “lipid”, there is no widely-accepted definition. General text books usually describe lipids in woolly terms as a group of naturally occurring compounds, which have in common a ready solubility in such organic solvents as hydrocarbons, chloroform, benzene, ethers and alcohols. They include a diverse range of compounds, like fatty acids and their derivatives, carotenoids, terpenes, steroids and bile acids. It should be apparent that many of these compounds have little by way of structure or function to relate them. In fact, a definition of this kind is positively misleading, since many of the substances that are now widely regarded as lipids may be almost as soluble in water as in organic solvents.

The lipids are large group of naturally occurring organic compounds that are related by their solubility in nonpolar organic solvents (e.g. ethet, chloroform, acetone and benzene) and general insolubility in water.

Lipids differ from the other classes of naturally occurring biomolecules (carbohydrates, proteins, and nucleic acids), they are more soluble ion- or weakly polar solvents (diethyl ether, hexane, dichloromethane) than in water. They include a variety of structural types, a collection of which is introduced in this chapter. In spite of the number of different structural types, lipids share a common biosynthetic origin in that they are ultimately derived from glucose. During one stage of carbohydrate metabolism, called glycolysis, glucose is converted to lactic acid. Pyruvic acid is an intermediate product.

 

Classification of lipids

Based on their chemical composition lipids are classified as;

Simple lipids: These are alcohol esters of fatty acids, which include; neutral lipids (glycerides), oils, wax, etc

Neutral lipids: Neutral fat consists mainly of triacylglycerols (triglycerides) which are composed of three fatty acids each in ester linkage with a single glycerol. Most neutral fats such as those in vegetable oils, butter and animal oil are mixture of simple and mixed triacylglycerols. Vegetable oils (corn oil) are liquid at room temperature due to high level of unsaturated fatty acids. These are converted industrially into solid fats by catalytic hydrogenation.

Biological waxes bee waxes are esters of long chain saturated and unsaturated fatty acids with long chain alcohols. Bee wax is secreted by the abdominal glands of the worker bees. The wax is used by worker bees for building the hive. Sebum or ear wax is secreted by cutaneous glands for lubricating ear drum. Paraffin wax is obtained from petroleum. It is used in cosmetic and polishes and making candles. Waxes serve as water repellants. Certain skin glands of vertebrates secrete waxes to protect skin. Aquatic birds secrete wax from preen gland to keep their feather water repellant.

Compound lipids. Lipids with additional groups are called compound lipids. The compound lipids includes;

Phospho lipids: These are triglyceride lipids in which one fatty acid is replaced by phosphate group. Some phospholipids also have nitrogenous compound such as choline in lecithin, ethanol amine in cephalin attached to the phosphate group. Phospholipids are amphipathic carrying both hydrophilic (water attracting) and hydrophobic (water repellant) non-polar groups.

Sphingolipids: These are composed of one molecule of the long chain amino alcohol sphingosine. Spingolipids are the large class of membrane lipids, which have a polar head group and two non-polar tails. When the head groups of sphingolipids contain one sugar, instead of phosphate, they are called as cerebrosides. The neural tissues are rich in cerebrosides.

 

•     Classification: Lipids can be divided into two major classes on the basis of whether they undergo hydrolysis reactions in alkaline (basic) solution. Saponifiable lipids can be hydrolyzed under alkaline conditions to yield salts of fatty acids. Nonsaponifiable lipids do not undergo hydrolysis reactions in alkaline solution.

•     The basis of the nature of the products obtained on hydrolysis lipids are mainly divided into three type: simple, compound and derived lipids.

•     1. Simple lipids. These are esters of fatty acids and alcohols and thus on hydrolysis give fatty acids and alcohols. They may be of two types.

•     а) Fats and oils. These are esters of fatty acids and glycerol (а trihydric alcohol). These are also known as glycerides.

•     b) Waxes. These are esters of long-chain fatty acids and long-chain monohydric alcohols or sterols.

•     2 Compound lipids. Compound lipids are esters of fatty acids and alcohols in combination with other compound and thus on hydrolysis give fatty acids, alcohol and other compounds. On the basis of the nature of the other group, compound lipids may again be of following types.

•     а) Phospholipids. These are fat like compounds containing phosphoric acid and а nitrogen base.

•     b) Glycolipids. These are compounds containing а fatty acid, а carbohydrate, а complex alcohol, and nitrogen, but nо phosphorus.

•     3. Derived lipids. These compounds although do not contain an ester linkage but are obtained by the hydrolysis of simple and compound lipids. They may be fatty acids, alcohols and sterols.

Lipids are organic compounds, found in living organisms that are soluble ionpolar organic solvents. Because compounds are classified as lipids on the basis of a physical property— their solubility in an organic solvent—rather than as a result of their structures, lipids have a variety of structures and functions, as the following examples illustrate:

Role of Lipids

The main purpose of lipids is to store energy.

Other very important function include:

–        structural elements (cell membrane)

–        dissolving fat soluble vitamins

–        transportation of some molecules through the blood

–        emulsifying agent (bile salts)

For many years, lipids were considered to be intractable and uninteresting oily materials with two main functions – to serve as a source of energy and as the building blocks of membranes. They were certainly not considered to be appropriate candidates for such important molecular tasks as intracellular signalling or local hormonal regulation. In 1929, George and Mildred Burr demonstrated that linoleic acid was an essential dietary constituent, but it was many years before the importance of this finding was recognized by biochemists in general. With the discovery by Bergström, Samuelsson and others in 1964 that the essential fatty acid arachidonate was the biosynthetic precursor of the prostaglandins with their effects on inflammation and other disease states, the scientific world in general began to realize that lipids were much more interesting than they had previously thought.

A major milestone was achieved in 1979 with the discovery of the first biologically active phospholipid, platelet-activating factor. At about the same time, there arose an awareness of the distinctive functions of phosphatidylinositol and its metabolites. Since then, virtually every individual lipid class has been found to have some unique biological role that is distinct from its function as a source of energy or as a simple construction unit of a membrane. Indeed it is now recognised that lipids in membranes function also in the trafficking of cellular constituents, the regulation of the activities of membrane proteins and signalling.

All multi-cellular organisms, use chemical messengers to send information between organelles and to other cells and as relatively small hydrophobic molecules, lipids are excellent candidates for signalling purposes. The fatty acid constituents have well-defined structural features, such as cis-double bonds in particular positions, which can carry information by binding selectively to specific receptors. In esterified form, they can infiltrate membranes or be translocated across them to carry signals to other cells. During transport, they are usually bound to proteins so their effective solution concentrations are very low, and they are can be considered to be inactive until they reach the site of action and encounter the appropriate receptor.

Storage lipids, such as triacylglycerols, in their cellular context are inert, and indeed esterification with fatty acids may be a method of de-activating steroidal hormones, for example, until they are actually required. In contrast, polar phospholipids have both hydrophobic and hydrophilic sites that can bind via various mechanisms to membrane proteins and influence their activities. Glycosphingolipids carry complex carbohydrate moieties that have a part to play in the immune system, for example. Lipids have been implicated in a number of human disease states, including cancer and cardiovascular disease, sometimes in a detrimental and sometimes in a beneficial manner. In short, every scientist should now be aware that lipids are just as fascinating as all the other groups of organic compound that make up living systems.

Functions of lipids

– The most important role of lipids is as а fuel. Much of the carbohydrates of the diet are converted to fat which is stored in various tissues and utilised at the time of requirement. Thus fat may be the major source of energy for many tissues. Actually, in some respects lipids (fats) are even superior to carbohydrates as source of energy.

    – Fatty acids with their flexible backbones can be stored in а much more compact form than the highly spatially oriented and rigid glycogen structure. Thus fat storage provides economy in both weight and space. In addition to the above three reasons there are two other reasons for fat storage as an excellent form of energy.

    – As it is insoluble in water, it has been carried to the fat depots by the specialised transport proteins in the plasma.

    – It remains as а stable and fixed reserve of energy until mobilized by enzymes which hydrolyse it to glycerol and fatty acids. The enzymes are under the control of various hormones and are activated under conditions where the body is involved in increased energy expenditure.

– Fat may also provide padding to protect the internal organs. Brain and nervous tissue are rich in certain lipids, а fact which indicates the importance of these compounds to life.

    – Some compounds derived from lipids are important building blocks of biologically active materials; е.g. acetic acid can be used by the body to synthesize cholesterol and related compounds (hormones).

    – Lipoproteins are constituents of cell walls. The lipids present in lipoproteins constituting the cell walls are of the types of phospholipids. Since lipids are water insoluble they act as ideal barrier for preventing water soluble materials from passing freely between the intra- and extra-cellular fluids.

    – One more important function of dietary lipids is that of supplying the so-called essential fatty acids although there are several functions (essential fatty acids (EFA), none of them are well defined.

Fatty Acids

The fatty acid is a carboxylic acid with a long unbranched aliphatic chain (“tail”), which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an eveumber of carbon atoms, from 4 to 28.

Saturated fatty acids

Saturated fatty acids are long-chain carboxylic acid containing only carbon–carbon single bonds.

Saturated fatty acids have §       Single C–C bonds. §       Molecules that fit closely together in a regular pattern. §       High melting points that make them solids at room temperature.

Unsaturated fatty acids

Unsaturated fatty acids are long-chain carboxylic acid containing one or more carbon–carbon double bonds.

Unsaturated fatty acids §       Have one or more double C=C bond §       Typically contain cis double bonds. §       Have low melting points. §       Are liquids at room temperature.

The two carbon atoms in the chain that are bound next to either side of the double bond can occur in a cis or trans configuration. In most naturally occurring unsaturated fatty acids all are cis bonds. Most fatty acids in the trans configuration (trans fats) are not found iature and are the result of human processing (e.g., hydrogenation).

 

 

 

Essential fatty acids

Fatty acids that are required by the body but cannot be made in sufficient quantity from other substrates, therefore must be obtained from food and are called essential fatty acids. Two fatty acids are essential in humans, linoleic acid and linolenic acid. They are widely distributed in plant oils.

Omega-3 and Omega-6 Fatty Acids

Commoames have been also developed; certain fatty acid names have been popularized by the media.  The acids can be named for how far the double bond lays away from the final tail carbon.  Linolenic acid has a double bond, three carbons from the fatty acids end. It is classified as an omega-3 fatty acid, the omega carbon being the terminal carbon and the bond being found on the third carbon from the end. Linoleic acid is an Ω-6 fatty acid. 

Unsaturated fats such as those in vegetable oils and fish are recognized as more beneficial to health than saturated fats.

Vegetables contain omega-6 acids, meaning the first double bond occur at carbon 6. Examples of omega-6 acids are linoleic and arachidonic acids.

Fish have high levels of omega-3 acids, meaning the first double bond occur at carbon 3. Examples of omega-3 acids include linolenic, eicosapentaenoic, and docosahexaenoic acids.

Cold-water fish are a source of omega-3 fatty acids.

Fats and oils

Fats and oils are naturally occurring mixtures of triacylglycerols, also called triglycerides.They differ in that fats are solids at room temperature and oils are liquids. We generally ignore this distinction and refer to both groups as fats. Triacylglycerols are built on a glycerol framework.

 

Simple triacylglycerines include similar fatty acids, mixed – different. All three acyl groups in a triacylglycerol may be the same, all three may be different, or one may be different from the other two.

Triglycerides (triglycerols) consist of          a glycerol esterifies with three fatty acids.

They a formed by dehydration reactions in which the three OH groups of a glycerol molecule react with the carboxylic acid groups of three different or same fatty acids to form three ester bonds and also three molecules of water.

These triglycerides (or triacylglycerols) are found in both plants and animals, and compose one of the major food groups of our diet. Tryglicerides that are solid or semisolid at room temperature are classified as fats, and occur predominantly in animals. Those triglycerides that are liquid are called oils and originate chiefly in plants, although triglycerides from fish are also largely oils.

As might be expected from the properties of the fatty acids, fats have a predominance of saturated fatty acids and oils are composed largely of unsaturated acids.

Triglycerides having three identical acyl chains, such as tristearin and triolein are called “simple”, while those composed of different acyl chains are called “mixed” (such as oleopalmitostearin).

        

Nomenclature, methods of getting of fats

For simple glycerides the name is made up of the name of the alcohol (glycerol) or its radical (glyceryl) and the name of the acid; or the name of the acid concerned is changed to suffix in. For mixed glycerides, the position and names of the acid groups are specified by Greek letters α, β, α’ or by the numerals 1, 2 and 3.

Methods of getting:

1.     O-acylation of alcohols;

2.     Allocation from plants: melting out, pressing or extraction by organic solvents.

Fatty acids are carboxylic acids with long hydrocarbon chains. Because they are synthesized from acetate, a compound with two carbon atoms, most naturally occurring fatty acids contain an eveumber of carbon atoms and are unbranched. Fatty acids can be saturated with hydrogen (and therefore have no carbon–carbon double bonds) or unsaturated (have carbon–carbon double bonds). Fatty acids with more than one double bond are called polyunsaturated fatty acids. Double bonds iaturally occurring unsaturated fatty acids are never conjugated — they are always separated by one methylene group. The physical properties of a fatty acid depend on the length of the hydrocarbon chain and the degree of unsaturation. As expected, the melting points of saturated fatty acids increase with increasing molecular weight because of increased Van-der-Waals interactions between the molecules

The most widespread fatty acids iatural oils and fats:

Double bonds are rigid structures, unsaturared acid molecules that contain them can occur in two isomeric forms: cis and trans. In cis-isomers, for example, similar or identical groups are on the same side of double bond (a). When such groups are on opposite sides of a double bond, the molecule is said to be a trans-isomer (b):

The double bonds in unsaturated fatty acids generally have the cis configuration. This configuration produces a bend in the molecules, which prevents them from packing together as tightly as fully saturated fatty acids. As a result, unsaturated fatty acids have fewer intermolecular interactions and, therefore, lower melting points than saturated fatty acids with comparable molecular weights . The melting points of the unsaturated fatty acids decrease as the number of double bonds increases. For example, an 18-carbon fatty acid melts at 69 °C if it is saturated, at 13 °C if it has one double bond, at if it has two -5 °C o double bonds, and at -11 °C if it has three double bonds.

Triacylglycerols, also called triglycerides, are compounds in which the three OH-groups of glycerol are esterified with fatty acids. If the three fatty acid components of a triacylglycerol are the same, the compound is called a simple triacylglycerol. Mixed triacylglycerols, on the other hand, contain two or three different fatty acid components and are more common than simple triacylglycerols. Not all triacylglycerol molecules from a single source are necessarily identical; substances such as lard and olive oil, for example, are mixtures of several different triacylglycerols.

Triacylglycerols that are solids or semisolids at room temperature are called fats. Fats are usually obtained from animals and are composed largely of triacylglycerols with either saturated fatty acids or fatty acids with only one double bond. The saturated fatty acid tails pack closely together, giving the triacylglycerols relatively high melting points, causing them to be solids at room temperature. Liquid triacylglycerols are called oils. Oils typically come from plant products such as corn, soybeans, olives, and peanuts. They are composed primarily of triacylglycerols with unsaturated fatty acids that cannot pack tightly together. Consequently, they have relatively low melting points, causing them to be liquids at room temperature.

Hydrolysis of а triacylglycerol is the reverse of the esterification reaction by which it wet formed. Complete hydrolysis of а triacylglycerol molecule always gives one glycerol molecule and three fatty acid molecules as products.

Chemical properties of fats

1). Hydrolysis of fats with alkali (e.g., sodium hydroxide) yields salts of the
fatty acids, and those of the alkali metals, such as sodium or potassium, are useig as soaps. Another name of this reaction – “saponification”:

The solubility of lipids ionpolar organic solvents results from their significant hydrocarbon component. The hydrocarbon portion of the compound is responsible for its “oiliness” or “fattiness.” The word lipid comes from the Greek lipos, which means “fat.”

Characterization of fats. The composition, quality and purity of а given oil or fat is determined by means of а number of physical and chemical tests. The usual physical tests include determination of m, р, specific gravity, viscosity, etc. while the chemical tests include determination of certain values discussed below.

•     1. Acid number. It is the number of milligrams of potassium hydroxide required to neutralise the free fatty acids in 1g. of the oil or fat. Thus it indicates the amount of free fatty acids present in oil or fat. А high acid value indicates а stale oil or fat stored under improper conditions.

•     2. Saponificatioumber. It is number of milligrams of potassium hydroxide required to completely hydrolysis of l g. of the oil or fat. Thus it is а measure of fatty acids present as esters in а given oil or fat. The saponification value gives an idea about the molecular weight of fat or oil. The saponificatioumber and molecular weight of an oil are inversely proportional to each other; thus high saponificatioumber indicates that the fat is made up of low molecular weight fatty acids and vice versa. It is also helpful in detecting adulteration of а given fat by one of the lower or higher saponfication value.

•     3. Iodine number. It is the number of grams of iodine that combine with 100 g. of oil or fat. It is а measure of the degree of unsaturation of а fat or oil; а high iodine number indicates а high degree of unsaturation of the fatty acids of the fat.

•     Difference between saponification and acid numbers named ether number which characterizes contain of  the remainders of fatty acids.

2). Oxidation of fates. Oxidation cases rancidity of fates. During oxidation form aldehydes with short carbon chain.

Oxidation at the soft conditions (water solution of KMnO4) cases formation of glycols. At the rigid conditions carbon skeleton destroys with formation of remainders of carbonic acids with shorter carbon chains.

Fats, which predominantly contain saturated fatty acids, by oxidation form ketones.

3). Hydrogenation. Some or all of the double bonds of polyunsaturated oils can be reduced by catalytic hydrogenation. Margarine and shortening are prepared by hydrogenating vegetable oils such as soybean oil and sunflower oil until they have the desired consistency. This process is called “hardening of oils.” The hydrogenation reaction must be carefully controlled, however, because reducing all the carbon–carbon double bonds would produce a hard fat with the consistency of beef tallow. Quantity of H2 in grams, which are necessary for hydration of 10kg of fats (hydratioumber) characterizes unsaturating of fat.

4). Addition of halogens.

As might be expected from the properties of the fatty acids, fats have a predominance of saturated fatty acids, and oils are composed largely of unsaturated acids. Thus, the melting points of triglycerides reflect their composition, as shown by the following examples. Natural mixed triglycerides have somewhat lower melting points, the melting point of lard being near 30 º C, whereas olive oil melts near -6 º C. Since fats are valued over oils by some Northern European and North American populations, vegetable oils are extensively converted to solid triglycerides (e.g. Crisco) by partial hydrogenation of their unsaturated components. Some of the remaining double bonds are isomerized (to trans) in this operation. These saturated and trans-fatty acid glycerides in the diet have been linked to long-term health issues such as atherosclerosis.

Compound Lipids.

As already mentioned, compound lipids are those which contain some chemical group in addition to fatty acids and an alcohol. On the nature of the additional chemical group, compound lipids are sub-divided into two main groups.

(a) Phospholipids: which contain а phosphate group.

(b) Glycolipids: which contain а carbohydrate.

Other classification divides the complex lipids into three main groups, viz.

 (1) Glycerophosphatides (glycerol phospholipids) – which are glycerol containing phospholipids.

(2) Phosphoinositides: which contain inositol (а hexahydric alcohol) as the base.

(3) Phosphosphingosides or sphingolipids (sphingosine lipids)- which contain sphingosine or dihydrosphingosine as the base.

            

Phospholipids (phosphatides). This group is the most abundant among the complex lipids It is found in every living cell and makes up as much as 70% of the complex lipid contents of the tissues. These substances are also known as phosphatides and are sometimes named as derivatives of the parent compound, а phosphatidic acid.

phosphatidic acid

Phospholipids may be defined as those lipids which yield on hysrolysis an alcohol, fatty acid, phosphoric acid, and а nitrogen base.

Functions of phospholipids. Phospholipids are involved in many functions. Sоme of these possible functions are listed below.

 (а) As а structural component. Phospholipids are said to be components of cellular membranes including membranes of mitochondria. The operation of the oxidative chain and oxidative chain phosphorylation in mitochondria is inactivated by removal of the phospholipids, which may be controlling or participating in the transport of metabolites from one side of the membrane to the other. Despite their structural differnces, all phospholipids have hydrophobic and hydrophilic domains. The hydrophobic domain is composed largely of the hydrocarbon chains of fatty acids; the hydrophilic domain, called a polar head group, contains phosphate and other charged or polar groups.

(b) In blood coagulation. Phospholipids having ethanolamine or serine as base are believed to function in the process of blood coagulation.

(c) In absorption and transport of lipids. Phospholipids may act as emulsifying agents during digestion and absorption of lipids and are believed to be important components of the coating of chylomicrons in the form of lipoproteins. Phospholipids are also involved in the transport of lipids in the blood. (A surface active agents is a subsstance that lowers the surface tension of a liquid, usually water, so that it spreads out over a surface.)

(d) Transport of ions. Some phospholipids help in the transport of inorganic ions mainly cations across the membrane.

Classification of phospholipids:    

  Phosphoacylglycerols are triesters of фусего1 in which two- ОН groups are esterified with fatty acids asnd one the third is esterified with phosphofic acid, which in turn is ecterified to an alcohol. The block diagram for а phosphoacylglycerol has the following general structure:

The most abundant phosphoacylglycerols have an amino alcohol (choline, ethanolamine, or serine) attached to the phosphate group. The structures of these three aminoalcohols, given in terms of the charged forms that they adopt ieutral solution, are

             

Choline                                                      Ethanolamine              Serine

Phosphoacylglycerols containing these three amino alcohols are respectively known as phosphatidylcholines, phosphatidylethanolamines, and phosphatidylserines. The fatty acid, glycerol, and phosphoric acid portions of а phosphoacylglycerol structure constitute а phosphatidyl group.

Although the general structural features of phosphoacylglycerols are similar in many respects to those of triacylglycerols, these two types of lipids have quite different biological functions. Triacylglycerols serve as storage molecules for metabolic fuel. Phosphoacylglycerols function almost exclusively as components of cell membranes and are not stored. А major structural difference between the two types of lipids, that of polarity, is related to their differing biological functions. Triacylglycerols are а nonpolar class of lipids, whereas phosphoacylglycerols are polar. In general, membrane lipids have polarity associated with their structures.

Further consideration of general phosphoacylglycerol structure reveals an additional structural characteristic of most membrane lipids. Let us consider а phosphatidylcholine containing stearic and oleic acids as our example. There are two important things to notice about this model:

(1) There is а “head” part, the choline and phosphate, and (2) there are two “tails,” the two fatty acid carbon chains. The head part is polar. The two tails, the carbon chains, are nonpolar.

All phosphoacylglycerols have а “head” “and two “tails. А simplified representation for this structure uses а circle to represent the polar head and two wavy lines to represent the nonpolar tails. The polar head group of а phosphoacylglycerol is soluble in water. The nonpolar tail chains are insoluble in water but soluble ionpolar substances. This dual-polarity feature, previously encountered when soaps were discussed, is а structural characteristic of most membrane lipids.

Phosphatidylcholines are also known as lecithins. There are а number of different phosphatidylcholines because different fatty acids may be bonded to the glycerol portion of the phosphatidylcholine structure. In general, phosphatidylcholines are waxy solids that form colloidal suspensions in water. Egg yolks and soybeans are good dietary sources of these lipids. Within the body, phosphatidylcholines are prevalent in cell membranes.

Periodically, claims arise that phosphatidylcholine should be taken as а nutritive supplement; some claims indicate it will improve memory. There is no evidence that these supplements are useful. The enzyme lecithinase in the intestine hydrolyzes most of the phosphatidylcholine taken orally before it passes into body fluids, so it does not reach body tissues. The phosphatidylcholine present in cell membranes is made by the liver; thus phosphatidylcholines are not essential nutrients.

The food industry uses phosphatidylcholines as emulsifiers to promote the mixing of otherwise immiscible materials. Mayonnaise, ice cream, and custards are some of the products they are found in. It is the polar – nonpolar (head – tail) structure of phosphatidylcholines that enables them to function as emulsifiers.

(a) Lecithins. Lecithins occur iearly all animal and plant organisms. In animals, lecithins are mainly found in egg yolk, brain, nerve tissues and sperm; while in plants they are particularly abundant in seeds and sprouts. The most important source of lecithins is egg yolk, from which its name is derived (Greek, lekithos  meaning yolk). Manу lecithins have been prepared synthetically. Lecithins are poorly crystalline substances They usually swell in water and form colloidal solutions. They are dextro-rotatory, and become inactive when heated in а sealed tube at 100 ⁰C.

Lecithins are esters of glycerol in whose molecule two hydroxyl groups have been estert6ed by fatty acids, while the third has been esterified by phosphoric acid which in turn has formed an ester with choline. The nature of fatty acids depends upon the source of the lecithins, thus the general structure of lecithins will be as below.

Lecithins in whose molecules the b-hydroxyt group of glycerol has been esterified by phosphoric acid are rare. Such lecithins are known as b-lecithins and produce optically inactive glycero b-phosphoric acid on hydrolysis.

glycero-b-phosphoric acid

As fаr as the nature of the fatty acids is concerned stearic, paimitic, oleic, linoleic, arachidonic and clupanodonic acids have been isolated from lecithins obtained trom animal tissues. Recent evidence indicates that in the above general formula of lecithins R is usually а saturated fatty acid, and R’ is usually an unsaturated fatty acid.

This is the most common form of phoipholipid, at least in animals. The lecithins are required for normal transport and utilization of other lipids, especially is the liver Anything which interferes with the synthesis of choline (а constituent of lecithins) will also restrict the synthesis of lecithins, and thus disturb the normal transportation of lipids to and from the liver. This will result in the accumulation of lipid material and thus give rise to the condition called “fatty liver”.

Certain enzymes in the snake venom can cause the hydrolysis of the unsaturated fatty acids on С₂ of phospholipids, resulting in the production of compounds known as lysolecithins t1ysocephalins, see (b) below). The latter compounds have strong hemolytic (red-blood cell destroying) action. If the hemolysis is extensive enough, it may result in the dearth of the victim of а snake bite.

The affinity of lecithins towards water со form emulsions makes lecithins an important constituent of protoplasm. Lecithin aids in the organization of the cell structure.

Commercially lecithin is prepared from soyabeans and has several important applications. Added to the chocolate it is used in making candy, it prevents the formation of white spots on the surface of chocolate creams. When added to oleomargarine it gives the product а consistency similar to that of butter.

(b) Cephalins (kephalins) are nearly similar to that of lecithins with the difference that they, unlike lecithins, contain а colamine (ethanolamine) residue (sometimes serine or myoinositol) instead of the choline residue. They are present in brain matter from which the nаme kephalin is derived (Greek kephale meaning heads). The separation of cephalins and lecithins is based on the fact that the cadmium chloride compound of’ the former is soluble while the corresponding salt of the latter is insoluble.

As in the lecithias, two fatty acids are present in the molecule, usually one saturated and the other unsaturated. Moreover, there are also two cephalins, viz. a– and b-. Following is the structure for an a-cephalin.

a-cephalin

Where, X= – an ethanolamine cephalin; X= – а serine cephalin

Stearic, oleic, linoleic, and arachidonic acids have been found as fatty acid constituents of the cephalins. Enzymes in snake venom can cause the formation of lysocepbalins. The cephaliris have been implicated in the process of blood coagulation (clotting). Cepbalins also play а fundamental role in the structure of living organism.

(c) Plasmalogeas.  These phospbolipids are characterized by the fact that on treatment with acid they form long chain fatty aldehydes The general structure of plasmalogens is the general structure of lecithin or cephalin in which one of the fatty acids is replaced by aldehydogenic group.

                  

Plasmalogens or plasmologens are widely distributed in animal tissues, especially in the myelin of brain heart nerve and skeletal muscle.

Cardiolipids are polymers of phosphatidic acids of any of the above type of phospholipids minus the base. These are isolated from beef heart extract and are said to be the active substances responsible for the serological test for syphilis.

Shingomyelins. These are composed of a complex basic dihydric amino alcohol, sphingosirse (sphingosinol) with a fatty acid in amide linkage on the amino group and the hosphorylcholine group attached by way of the terminal alcohol group. Thus they differ chemically from other phospholipids in the following two important respects.

All lipids derived from sphingosine have (1) а fatty acid connected to the – NH, group via an amide linkage, and (2) а group attached to the – ОН group on the terminal carbon atom via an ester linkage.

Note again, as in phosphoacylglycerols and waxes, the structural features of а head and two tails. For sphingolipids, the fatty acid is one of the tails, and the long carbon chain of sphingosine itself s the other tail. The “additional component” is the heal, and it is а phosphoric acid – choline group.

  

Sphingolipids are the second major class of nonglycerol-based saponifiable lipids. Like phosphoacylglycerols, they are polar lipids and are major constituents of cell membranes.

Sphingolipids have structures based on the long-chain amino dialcohol sphingosine. А sphingolipid is а saponijiable lipid derived from the amino dialcohol sphingosine. The structure of sphingosine is:

Phytospingosine is found in plant spingolipids. The core structure of each type of spingolipid is ceramide, a fatty acidamide derivative of shingosine. In shingomyelin, ceramide is esterified to phosphatidylcholine or phosphatidylethanolamine. Sphingomyelin is found in most animal cell membranes. However, as its name suggests, spingomyelin is found in greatest abundance in the myelin sheath of nerve cells. (The myelin sheath is found by successive wrappings of the cell membrane of a specialized myelinating cell around a nerve cell axon. It facilitates the rapid transmission of nerve impulses).The ceramides are also precursors for the glycolipids, sometimes referred to as the glycosphingolipids. Clicolipids differ from spingomyelin in that they contaio phosphate. In glycolipids a monosaccharide, disaccharideor oligosaccharide is attached to aceramede through an O-glycosidic linkage. The most important glycolipid classes are cerebrosides, the sulfatides, and the gangliosides. Cerebrosides are shingolipids in which the head group is a monosaccharide.Galactocerebrosides, the most common axample of this class, are almost entifely found in thecell membranes of the brain. if a cerebroside is sulfated, it is referred to as a sulfatide. Sulfatidesare negatively charged at physiological pH. Spingolipids that possess oligosaccharide groups with one or more sialic acid residues are called gangliosides. Althhough gangliosides were first isolated form nerve tissue, they also occur in most other animal tissues. The names of individual gangliosides include subscript letter and numbers. The letters M, D and T indicate whether the molecule contains one, two, or three sialic residues, respectively. The number notation designates the sequence of sugars that are attached to ceramide. The structure of the Tay-Sachs ganglioside. The rol of glycolipids is still unclear. Certain glycolipid molecules have been implicated in the binding of bacterial toxins, as well as bacterial cells, to animal cell membranes. For example, the toxins that are responsible for cholera, tetanus, and botulism bind to glycolipid cell membrane receptors. Bacteria that have been shown to bing to glycolipid receptors include Eschefichia coli, Streptococcus pneumoniae, and Neisseria gonorrhoea, the causative agents of urinary tract infections, pneumonia, and gonorrhea respectively.

Following structure has been assigned to shinomyelin on the basis of the usual hydrolysis.

Three fatty acids namely stearic, lignoceric or nervonic were obtained from а pure sphingomyelin fraction.

Like other phospholipids, it а1sо occurs practically in all animal tissues particularly in brain and spinal cord and in plant seeds. It is very sparingly soluble in ether, and thus can be easily separated from the lecithins and cephalins.

Cerebrosides and Gangliosides. Some sphingosine-based membrane lipids have а small carbohydrate as the head group. Cerebrosides, the simplest of such carbohydrate-containing lipids, usually have а glucose or galactose as the carbohydrate unit. The cerebrosides, as the name suggests, occur primarily in the brain (7 % of dry mass) and in the myelin sheath of nerves. Gangliosides contain more complex carbohydrate heads; up to seven monosaccharide units are present. These substances occur in the gray matter of the brain as well as in the myelin sheath.

The specific structure of the cerebroside in which stearic acid (18:0) is the fatty acid and galactose is the monosaccharide is

The accompanying Chemistry at а Glance briefly outlines the classification of saponifiable lipids.

Galactolipias occur in considerable amounts in the white matter of the brain and of all nervous tissue. They usually occur in the amorphous state. but are also known as liquid crystals. They are insoluble in ether but soluble in hot alcohol. On hydrolysis, give а fatty acid, sphingosinol, and а sugar, usually galactose. As mentioned earlier, there are four individual members of this group which differ only in the nature of their fatty acids. The general structural formula for galactolipids is as below.        

The sphingosine-fatty acid moieiy is called а ceramde. In addition to the above compound lipids there are globosides, hematosides and gangliosides. They are structurally similar to glycosides with the only difference that in the former the sugar residues are acetylated amino sugars, е.g. D-galactosamine, in the middle one they are sialic acid while in the latter acetylated amino sugars and sialic acid both are present.

Nonsaponifiable Lipids do not undergo hydrolysis in alkaline solution. Their structures are much different from those of the saponifiable lipids; neither ester nor amide linkages are present.

Nonsaponifiable Lipids: steroids, eicosanoids, terpenes, pheromones, fat-soluble vitamins.

Steroids are lipids with structures that are based on а fused-ring system involving three 6-membered rings and one 5-membered ring. The fused-ring system of steroids, called а steroid nucleus, has the following structure:

Steroid nucleus

Note that the rings are customarily labeled with letters and each carbon atom is labeled with а number.

Numerous steroids have been isolated from plants, animals, and human beings. Location of double bonds within the fused-ring system and the nature and location of substituents distinguish one steroid from another. Most steroids have an oxygen functional group (= О or – ОН) at carbon 3 and some kind of side chain at carbon 17. Many also have а double bond from carbon 5 to either carbon 4 or carbon 6.

Cholesterol is the most abundant steroid in the human body. The name cholesterol has the -ol ending because it is an alcohol, with an – ОН group on carbon 3 of the steroid nucleus. In addition, cholesterol has methyl groups bonded to carbon atoms 10 and 13 and а small branched hydrocarbon chain on carbon 17.

Within the human body, cholesterol is found in cell membranes (up to 25 % by mass), nerve tissue, and brain tissue (about 10% by dry mass), and it is the main component of gallstones. Human blood plasma contains about 50 mg of free cholesterol per 100 mL and about 170 mg of cholesterol esterified with various fatty acids.

А space-filling model of the cholesterol molecule shows the rather compact nature of this molecule. The “head and two tails” arrangement found in many lipids is not present. The lack of а large polar head causes cholesterol to have limited water solubility. The – ОН group on carbon 3 is considered the head of the molecule.

Cholesterol plays а vital biological role in chemical synthesis within the human body. It is the starting material for the synthesis of numerous steroid hormones, vitamin D, and bile salts. Its presence in the body is essential to life.

It is important to note that cholesterol is usually stored within cells as a fatty acid ester. The esterification reaction is catalyzed by the enzyme acyl CoA: cholecterol acyltransferase (ACAT), located on the cytoplasmic face of the endoplasmic reticulum.

Coadioac glycosides are among the most interesting steroid derivatives recall that glycosides are carbohydrate-containing acetals or ketals. Although several cardiac glycosides are axtremely toxic (ouabain, obtained from the seeds of the plant Strophanthus groups), others have valuablemedical properties. For example, digitalis, an axtract of the dried leaves of Digitalis purpurea (the fixglove plant), is a time-honored stimulator of cardiac muscle contraction. Digitoxin, the major “cardiotonic” glycoside in digitalis, is used in the treatment of congestive heart failure. It is important to note that in higher than therapeutic doses, digitoxin is extremely toxic. Both ouabain and digitoxin are inhibitors of the Na⁺ -K⁺ATPase.

The human body, mainly within the liver, synthesizes about 1 gram of cholesterol each day, an amount suf5cient to meet the body’s biosynthetic needs. Therefore, cholesterol it not necessary in the diet. When we ingest cholesterol, the amount synthesized by the body is reduced. However, the reduction is less than the amount ingested. Therefore, total body cholesterol level increases with dietary cholesterol level.

Medical science now considers high blood cholesterol, along with high blood pressure and smoking, as the major risk factors for cardiovascular disease (CVD). High blood cholesterol contributes to atherosclerosis, the main form of CVD, which is characterized by the buildup of plaque along the inner walls of the arteries. Plaque is а mound of lipid material mixed with smooth muscle cells and calcium. Much of the lipid material in plaque is cholesterol. Extensive plaque formation leads to hardening of the arteries. Plaque deposits in the arteries that serve the heart reduce blood flow to the heart muscle and can lead to а heart attack.

People who want to reduce their level of dietary cholesterol should reduce the amount of animal products they eat (meat, dairy products, etc.) and eat more fruit and vegetables. Plant foods contaio cholesterol; it is found only in foods of animal origin.

Derived Lipids. Derived lipids are those which although do not contain any ester linkage but may be considered to have been derived from naturally occurring esterified materials. In simple words, we can say that derived lipids are substances formed on the hydrolysis of simple or compound lipids which still retain the properties of this class of compounds. Derived lipids may be of following types.

1. Fatty acids. Saturated and unsaturated.

2. Alcohols. Alcohols of high molecular weight but not glycerol. These may again be of following types.

(a) Aliphatic alcohols such as cetyl, stearyl and myricyl alcohols

(b) Sterols. These contain phenanthrene nucleus important examples are cholesterol, ergosterol and stigmasterol.

(c) Alchols having b-ionone ring. These include vitamin A₁ and carotenols (е.g., lutein and zeaxanthin).

3. Hydrocarbons. These include aliphatic hydrocarbons, carotenes, and squalene.

4. Certain vitamins. These include vitamins D, E and К.

5. Steroids hormones.

6. Bile acids.  

The liver secretes а clear, golden-yellow, viscous fluid known as bile. It is stored in the gall bladder and is mainly useful for digestive system. Bile consists of inorganic (chiefly НСО₃^–, С1^–, Na⁺, К⁺ etc.) ions as well as organic compounds. Among organic compounds the main constituents are bile acids, bile pigments, lipids, fatty acids and cholesterol.

The bile acids are present as the sodium salt of amide with glycine or taurine, e.g. sodium glycocholate (glycine+cholic acid) and taurocholate (taurine + cholic acid). Bile acids are the hydoxy derivatives of either cholanic or allocholanic acid and dehydration followed by reduction of the bile acids give the latter (cholanic or allocholanic acid).

The bile acids form molecular compounds with various substances, е.g. deoxycholic acid forms such complexes with fatty acids which are known as choleic acids.

Cholic acid

Bile salts are emulsifying agents that make dietary lipids soluble in the aqueous environment of the digestive tract. During digestion, bile salts are released into the intestine from the gallbladder, where they help digestion by emulsifying (solubilizing) fats and oils. Their mode of action is much like that of soap during washing.

Bile salts are cholesterol oxidation products. They are trihydroxy cholesterol derivatives in which the carbon-17 side chain has been oxidized to а carboxylic acid. This acid side chain is then bonded to an amino acid through an amide linkage. The two principal bile salts are sodium glycocholate (glycine is the amino acid) and sodium taurocholate (taurine is the amino acid).

Sodium glycocholate

Sodium taurocholate

Cholesterol, an important molecule in animals, is a representative example of the steroids. In addition to its role as an essential component in animal cell membranes, cholecterol is a precursor in the biosynthesis of all steroid hormones, vitamin D. and bile salts:

Functions of bile acids. The important functions of the bile acids may be summarised as below.

(a) They facilitate digestion of fats by emulsifying them and thereby increasing the surface area of the material for pancreatic enzymes.

(b) They also activate the enzyme choiesterol esterase and pancreatic lipase.

 (c) They help in the absorption of cholesterol, fat soluble vitamins (А, D, Е, F, К), etc. by forming water soluble complexes.

(d) They also keep cholesterol in solution, if the ratio between bile acids and cholesterol falls than the normal, cholesterol is precipitated and forms gallstones in liver, and gallbladder.

The bile acid in the bile entering the intestine are rapidly absorbed into the blood, taken back by the liver and reutilized. This is called enierohepatic circularion of bile salts. Unabsorbed bile acids are attacked by bacteria and decomposed into various products which are excreted in faeces.

Steroid Hormones. Hormones are chemical messengers produced by ductless glands. They serve as а means of communication between various tissues. Many, but not all, hormones in the human body are steroids. Cholesterol is the ultimate starting material for the production of all steroid hormones, so they contain its characteristic system of four fused rings. Steroid hormone synthesis is always а multistep process.

There are two major classes of steroid hormones: the sex hormones, which control reproduction and secondary sex characteristics, and the adrenocorttcal hormones, which regulate numerous biochemical processes in the body.

The sex hormones can be classified into three major groups:

1. Estrogens — the female sex hormones

2. Androgens — the male sex hormones

3. Progestins — the pregnancy hormones

Estrogens are synthesized in the ovaries and adrenal cortex and are responsible for the development of female secondary sex characteristics at the onset of puberty and for regulation of the menstrual cycle. They also stimulate the development of the mammary glands during pregnancy and induce estrus (heat) in animals.

Androgens are synthesized in the testes and adrenal cortex and promote the development of secondary male characteristics. They also promote muscle growth.

Progestins are synthesized in the ovaries and the placenta and prepare the lining of the uterus for implantation of the fertilized ovum. They also suppress ovulation.

The fact that seemingly minor changes structure effect great changes in biofunction points out, again, the extreme specificity of the enzymes that control biochemical reactions.

Increased knowledge of the structures and functions of sex hormones has led to the development of а number of synthetic steroids whose actions often mimic those of the natural hormones. Among the best known of the synthetic steroids are oral contraceptives and anabolic agents.

Estradiol – the principal estrogen; responsible for secondary female characteristics.

Testosterone the principal androgen; responsible for secondary male characteristics.

Progesterone the principal progestin; prepares the uterus for pregnancy

Oral contraceptives are used to suppress ovulation as а method of birth control. Generally, а mixture of а synthetic estrogen and а synthetic progestin is used. The synthetic estrogen regulates the menstrual cycle, and the synthetic progestin prevents ovulation, thus creating а false state of pregnancy. Compare its structure to that of progesterone (the real hormone); the structures are very similar.

The second major group of steroid hormones consists of the adrenocortical hormones,

Produced by the adrenal glands, small organs located on top of each kidney, at least 2g different hormones have been isolated from the There are two types of adrenocortical hormones.

1. Mineralocorticoidx control the balance of Na⁺ and К⁺ ions in cells.

2. Glucocorticoids control glucose metabolism and counteract inflammation.

The major mineralocorticoid is aldosterone, and the major glucocorticoid is cortisol (hydrocortisone). Cortisol is the hormone synthesized in the largest amount by the adrenal glands. Cortisol and its synthetic ketone derivative cortisone exert powerful anti-inflammatory effects in the body. Both cortisone and prednisolone, а similar synthetic derivative, are used as prescription drugs to control inflammatory diseases such as rheumatoid arthritis. adrenal cortex (the outer part other glandi),

Aldosterone (а mineralocorticoid)

 Cortisol (а glucocorticoid)

Cortisone (an anti-inflammatory drug)

Prednisolone (an anti-inflammatory drug)

Eicosanoids are oxygenated derivatives of polyunsaturated 20-carbon fatty acids. The metabolic precursor of most eicosanoids is arachidonic acid, the 20:4 fatty acid. The name eicosanoid is derived from the Greek word eikos, which means “twenty.”

Almost all cells, except red blood cells, produce eicosanoids. These substances, like hormones, have profound physiological effects at extremely low concentrations. Eicosanoids are hormone-like molecules rather than true hormones, because they are not transported in the bloodstream to their site of action, as are true hormones; instead, they exert their effects in the tissues where they are synthesized. The physiological effects of eicosanoids include mediation of:

1. The inflammatory response, а normal response to tissue damage

2. The production of раin and fever

3. The regulation of blood pressure

4. The induction of blood clotting

5. The control of reproduction functions, such as induction of labor

6. The regulation of the sleep/wake cycle

There are three principal types of eicosanoids: prostaglandins, thromboxanes, and leukotrienes.

Prostaglandins are 20-carbon fаtty acid derivatives that contain а cyclopentane ring and oxygen-containing functional groups. Twenty-carbon fatty acids are converted into а prostaglandin structure when the eighth and twelfth carbon atoms of the fatty acid become connected to form а five-membered ring.

Prostaglandins are named after the prostate gland, which was first thought to be their only source. Today, more than 20 prostaglandins have been discovered in а variety of tissues in both males and females.

Within the human body, prostaglandins are involved in many regulatory functions, including raising body temperature, inhibiting the secretion of gastric juices, relaxing and contracting smooth пinзсlе, directing water and electrolyte balance, intensifying pain, and enhancing inflammation responses. Aspirin reduces inflammation and fever because it inactivates the enzyme needed for prostaglandin synthesis.

Thromboxanes are 20-carbon fatty acid derivatives that contain а cyclic ether ring and oxygen-containing functional groups. As with prostaglandins, the cyclic structure involves а bond between carbons 8 and 12. An important function of thromboxanes is to promote the formation of blood clots. Thromboxanes are produced by blood platelets and promote platelet aggregation.

Leukotrienes are 20-carbon fatty acid derivatives that contain three conjugated double bonds and hydroxy groups. Fatty acids and their derivatives do not normally contain conjugated double bonds, as is the case in leukotrienes. Leukotrienes are found in leukocytes (white blood cells). Their source and the presence of the three conjugated double bonds account for their name. Various inflammatory and hypersensitivity (allergy) responses are associated with elevated levels of leukotrienes. The development of drugs that inhibit leukotriene synthesis has been an active area of research.

 Isoprenoids are not synthesized form isoprene (methylbutadiene). Instead, their biosynthetic pathways all begin with the formation of isopentenyl pyrophosphate from acetyl-CoA. 

The isoprenoids consist of terpenes and steroids. Terpenes are an enormous group of molecules that are found largely in the “essential oils” of plants. Steroids are derivatives of complex hydrocarbon ring system.

The terpenes are classiffied according to the number of isoprene residues they contain. Monoterpenes are composed of two isoprene units. Geraniol is a monoterpene found in oil of geranium. Terpenes that contain three isoprenes are referred to as sesquiterpenes. Fernesene, an important constituent of oil of citronella (a substance used in soap and perfumes), is a sesquterpene. Phytol, a plant alcohol, is an example of the diterpenes, molecules composed of four isoprene units. Squalene, which is found in large quantities in shark liver oil as well as olive oil and yeast, is a prominent example of the triterpenes. Squalene is an intermediate in the synthesis f the steroids). Carotenoids, the orange-colored pigment found  in most plants, are the only example of the tetraterpenes (molecules composed of eight isoprene units). The cerotenes are hydrocarbon members of this group. The xanthophylls are oxygenated derivatives of the carotenes. Polyterpenes are high-molecular-weight molecules composed of hudreds or thousands of isoprene units. natural rubber is a polyterpene composed of between 3000 and 6000isoprene units.

Severol important biomolecules are composed of nonterpene components attached to isoprenoid groups (aften referred to as prenyl or isoprenyl groups). Examples of these biomolecules, referred to as mixed terpenoids, include vitamin E (a-tocopherol, ubiquione, vitamin K, and some cytokinins(plant hormones).

It has recently become apparent that a variety of proteins in eukaryotic cells are covalently attached to prenyl groups that are most often involved in his process, referred to as prenylation, are farnesyl and geranylgeranyl groups. The function of protein prenylation is not clear. There is some avidence that it plays a role in the control of cell growth. For example, Res proteins, a group of cell growth regulators, are activated by prenylation reactions.

            A vitamin is an organic compound required as a nutrient in tiny amounts by an organism. The term ‘vitamin’ first became popular in the early 1800’s as a contraction of the words ‘vital’ and ‘mineral’, though the actual meaning of the word has developed somewhat since that time. A compound is called a vitamin when it cannot be synthesized in sufficient quantities by an organism, and must be obtained from the diet. Thus, the term is conditional both on the circumstances and the particular organism. For example, ascorbic acid functions as vitamin C for some animals but not others, and vitamins D and K are required in the human diet only in certain circumstances. The term vitamin does not include other essential nutrients such as dietary minerals, essential fatty acids, or essential amino acids, nor does it encompass the large number of other nutrients that promote health but are otherwise required less often.

Vitamins are classified by their biological and chemical activity, not their structure. Thus, each “vitamin” may refer to several vitamer compounds that all show the biological activity associated with a particular vitamin. Such a set of chemicals are grouped under an alphabetized vitamin “generic descriptor” title, such as “vitamin A”, which includes the compounds retinal, retinol, and four known carotenoids. Vitamers are often inter-converted in the body. Vitamins have diverse biochemical functions, including function as hormones (e.g. vitamin D), antioxidants (e.g. vitamin E), and mediators of cell signaling and regulators of cell and tissue growth and differentiation (e.g. vitamin A). The largest number of vitamins (e.g. B complex vitamins) function as precursors for enzyme cofactor bio-molecules (coenzymes), that help act as catalysts and substrates in metabolism. When acting as part of a catalyst, vitamins are bound to enzymes and are called prosthetic groups. For example, biotin is part of enzymes involved in making fatty acids. Vitamins also act as coenzymes to carry chemical groups between enzymes. For example, folic acid carries various forms of carbon group – methyl, formyl and methylene – in the cell. Although these roles in assisting enzyme reactions are vitamins’ best-known function, the other vitamin functions are equally important.^[7]

Until the 1900s, vitamins were obtained solely through food intake, and changes in diet (which, for example, could occur during a particular growing season) can alter the types and amounts of vitamins ingested. Vitamins have been produced as commodity chemicals and made widely available as inexpensive pills for several decades, allowing supplementation of the dietary intake.

List of vitamins

Each vitamin is typically used in multiple reactions and, therefore, most have multiple functions.

Vitamin generic descriptor name	Vitamer chemical name(s) (list not complete)	Solubility	Recommended dietary allowances (male, age 19–70)	Deficiency disease	Upper Intake Level (UL/day)	Overdose disease
Vitamin A	Retinol, retinal, various retinoids, and four carotenoids)	Fat	900 µg	Night-blindness and Keratomalacia	3,000 µg	Hypervitaminosis A
Vitamin B1	Thiamine	Water	1.2 mg	Beriberi, Wernicke-Korsakoff syndrome	N/D	Drowsiness or muscle relaxation with large doses.
Vitamin B2	Riboflavin	Water	1.3 mg	Ariboflavinosis	N/D
Vitamin B3	Niacin, niacinamide	Water	16.0 mg	Pellagra	35.0 mg	Liver damage (doses > 2g/day) and other problems
Vitamin B5	Pantothenic acid	Water	5.0 mg	Paresthesia	N/D	Diarrhea; possibly nausea and heartburn.
Vitamin B6	Pyridoxine, pyridoxamine, pyridoxal	Water	1.3–1.7 mg	Anemia peripheral neuropathy.	100 mg	Impairment of proprioception, nerve damage (doses > 100 mg/day)
Vitamin B7	Biotin	Water	30.0 µg	Dermatitis, enteritis	N/D
Vitamin B9	Folic acid, folinic acid	Water	400 µg	Deficiency during pregnancy is associated with birth defects, such as neural tube defects	1,000 µg	May mask symptoms of vitamin B12 deficiency; other effects.
Vitamin B12	Cyanocobalamin, hydroxycobalamin, methylcobalamin	Water	2.4 µg	Megaloblastic anemia	N/D	No known toxicity
Vitamin C	Ascorbic acid	Water	90.0 mg	Scurvy	2,000 mg	Vitamin C megadosage
Vitamin D	Ergocalciferol, cholecalciferol	Fat	5.0 µg–10 µg	Rickets and Osteomalacia	50 µg	Hypervitaminosis D
Vitamin E	Tocopherols, tocotrienols	Fat	15.0 mg	Deficiency is very rare; mild hemolytic anemia iewborn infants.	1,000 mg	Increased congestive heart failure seen in one large randomized study.
Vitamin K	phylloquinone, menaquinones	Fat	120 µg	Bleeding diathesis	N/D	Increases coagulation in patients taking warfarin.

References:

Main:

1. Clayden Jonathan. Organic Chemistry. Jonathan Clayden, Nick Geeves, Stuart Warren // Paperback, 2nd Edition. – 2012. – 1234 p.

2. Bruice Paula Y.  Organic Chemistry / Paula Y. Bruice // Hardcover, 6th Edition. – 2010. – 1440 p.

3. Brückner Reinhard. Organic Mechanisms – Reactions, Stereochemistry and Synthesis / Reinhard Brückner // Hardcover, First Edition. – 2010. – 856 p.

4. Moloney Mark G. Structure and Reactivity in Organic Chemistry / Mark G. Moloney // Softcover, First Edition. – 2008. – 306 p.

5. Carrea Giacomo. Organic Synthesis with Enzymes in Non-Aqueous Media / Giacomo Carrea, Sergio Riva // Hardcover, First Edition. – 2008. – 328 p.

6. Smith Michael B. March’s Advanced Organic Chemistry. Reactions, mechanisms, and structure / Michael B. Smith, Jerry March // Hardcover, 6th Edition. – 2007. – 2384 p.

7. Carey Francis A. Advanced Organic Chemistry / Francis A. Carey, Richard A. Sundberg // Paperback, 5th Edition. – 2007. – 1199 p.

 

Additional:

 

1. Francotte Eric. Chirality in Drug Research / Eric Francotte, Wolfgang Lindner //
Hardcover, First Edition. – 2006. – 351 p.

2. Quin Louis D. Fundamentals of Heterocyclic Chemistry: Importance in Nature and in the Synthesis of Pharmaceuticals / Louis D. Quin, John Tyrell // Hardcover, 1st Edition. – 2010. – 327 p.

3. Zweifel George S. Modern Organic Synthesis – An Introduction / George S. Zweifel, Michael H. Nantz // Softcover, 1st Edition. – 2007. – 504 p.

4. K. C. Nicolaou. Molecules that changed the World / Nicolaou K. C., Tamsyn Montagnon // Hardcover, First Edition. – 2008. – 385 p.

5. Mundy Bradford P. Name Reactions and Reagents in Organic Synthesis / Bradford P. Mundy, Michael G. Ellerd, Frank G. Favaloro // Hardcover, 2nd Edition. – 2005. – 886 p.

6. Li Jie Jack. Name Reactions. A Collection of Detailed Reaction Mechanisms / Jie Jack Li // Hardcover, 4th Edition. – 2009. – 621 p.

7. Gallego M. Gomez. Organic Reaction Mechanisms / M. Gomez Gallego, M. A. Sierra // Hardcover, First Edition. – 2004. – 290 p.

8. Sankararaman Sethuraman. Pericyclic Reactions – A Textbook / Sethuraman Sankararaman // Softcover, First Edition. – 2005. – 418 p.

9. Tietze Lutz F. Reactions and Syntheses / Lutz F. Tietze, Theophil Eicher, Ulf Diederichsen // Paperback, First Edition. – 2007. – 598 p.

10. Olah George A. Superelectrophiles and Their Chemistry / George A. Olah, Douglas A. Klumpp // Hardcover, First Edition. – 2007. – 301 p.

11. Grossmann Robert B. The Art of Writing Reasonable Organic Reaction Mechanisms / Robert B. Grossmann // Hardcover, 2nd Edition. – 2003. – 355 p.

12. Cole Theodor C.H. Wörterbuch Labor – Laboratory Dictionary / Theodor C.H. Cole // Hardcover, 2nd Edition. – 2009. – 453 p.