Lipids: An Overview of Structure, Function and Importance

Lipids The term lipids are refers to a collection of organic molecules of varying chemical compositions present in plant and animal tissues, they are grouped together on the basis of their solubility in non-polar solvents such as acetone, chloroform, and benzene. Biomedical importance of...

Lipids The term lipids are refers to a collection of organic molecules of varying chemical compositions present in plant and animal tissues, they are grouped together on the basis of their solubility in non-polar solvents such as acetone, chloroform, and benzene. Biomedical importance of lipids:- 1. Act as energy source and storage in the body. 2. Lipids supply essential fatty acids in diet. 3. They serve as a source of fat soluble vitamins (Vitamin A, D, E and K). 4. Lipids act as protective layer for the vital organs. 5. Lipids act as insulator because fat stored beneath the skin (subcutaneous fat). 6. Lipids include a number of hormones, of which the most important are steroids and prostaglandins. 7. Phospholipids are important constituents of cell membranes. 8. Lipoproteins are carriers of Triglycerides, phospholipids and cholesterol in the blood. Lipids are commonly subdivided to four main groups: 1. Fatty acids (saturated and Unsaturated). 2. Glycerides (glycerol containing lipid). 3. Nonglyceride lipids (sphingolipids, steroids and waxes). 4. Complex lipid (lipoproteins). 1- Fatty acids: Fatty acids consist of a long carbon chain (also called an acyl chain) with a carboxylic acid at one end, they are unbranched linear molecules. Fatty acids in most biological systems are synthesized by serial addition of two carbon units, to produce an even number carbon atom fatty acid. Over 100 fatty acids have been isolated from various lipids. The naturally occurring fatty acids are carboxylic acids with un-branched hydrocarbon chains of 4–24 carbon atoms. They are present in all organisms as components of fats and membrane lipids. In these compounds, they are esterified with alcohols (glycerol, sphingosine, or cholesterol). However, fatty acids are also found in small amounts in unesterified form. In this case, they are known as free fatty acids (FFAs). The numbering of carbons in fatty acids begins with the carbon of the carboxylate group. Depending on the absence, or presence of double bonds, they are classified into saturated and unsaturated fatty acids. Saturated fatty acids:- Fatty acids that do not contain double bond in their structure are called saturated fatty acids. Palmatic acid CH3(CH2)14COOH Stearic acid CH3(CH2)16COOH Δ nomenclature The majority of fatty acids are linear molecules with carboxylic acids at one end. The only differences between fatty acid molecules are therefore the number of carbons, the number and position of double bonds. The symbol “Δ” is used to indicate the presence and position of the double bond. The positions of any double bonds are specified by superscript numbers following the Δ. Unsaturated fatty acids: Monounsaturated fatty acids contain a single double bond, while others containing more than one site of unsaturation which called poly Unsaturated fatty acids. for example: Palmitoleic acid [16:1Δ9] Oleic acid [18:1Δ9] (it mean an 18 carbon fatty acid with one double bond between the C9-C10). The first double bond added to saturated fatty acid is nearly always in the Δ9 position by an enzyme system Δ9 desaturase, therefore palmitoleic and oleic acids are non essential fatty acids. (Essential fatty acids are fatty acids that have to be supplied in the diet.) and only linoleic and linolenic acids are considered to be essential fatty acids. Polyunsaturated fatty acids: Linoleic acid [18:2Δ9.12] Two double bonds between C9-C10 and C12-C13. Linolenic acid [18:3Δ9.12.15] Contain three double bonds between C9-C10, C12-C13 and C15-C16. Arachidonic acid [20:4Δ5.8.11.14] Contains four double bonds between C5-C6, C8-C9, C11-C12 and C14-C15. For unsaturated fatty acid there are two possible isomers cis and trans, usually only the cis forms are found in natural lipids. Branched fatty acids only occur in bacteria. Omega ω nomenclature Another numbering system that is frequently used by nutritionists is the omega system. With this system the carbon atom farthest from the carboxyl carbon (the methyl carbon) is called omega (ω); and counting back along the chain of carbon atoms gives ω1, ω2, ω3..... For example a fatty acid with a double bond between the third and fourth carbon atoms from the methyl carbon is called an ω3 fatty acid. Omega ω nomenclature The position of the first double bond is indicated after the (ω). Often in the ω system, the other double bonds are not specified. The nomenclature has the advantage that the position numbers of the double bonds do not change with elongation since the new carbons are added to the carboxylate end. By using this nomenclature, oleic acid is an ω9 fatty acid, and linoleic acid is an ω6 fatty acid containing two double bonds while Linolenic acid is an ω3 fatty acid containing three double bonds. Humans can synthesize ω9 fatty acids; plants and some animals (especially fish) can synthesize ω6 and ω3 fatty acids as well. Omega is the last letter in the Greek alphabet. Essential fatty acids Two fatty acids are dietary essentials in humans because of our inability to synthesize them: linoleic acid, which is the precursor of ω-6 arachidonic acid, the substrate for prostaglandin synthesis, and α-linolenic acid, the precursor of other ω-3 fatty acids important for growth and development. [Note: Arachidonic acid becomes essential if linoleic acid is deficient in the diet.] Many clinical studies have shown positive roles for omega-3 fatty acids in cancer; cardiovascular diseases; and more recently, in various mental illnesses. These fatty acids are known to have effects against inflammation, platelet aggregation, hypertension, and hyperlipidemia. These beneficial effects may be mediated through several distinct mechanisms, including alterations in cell membrane composition and function, gene expression, or eicosanoid production. Melting point of fatty acid: Melting points are strongly influenced by the length and degree of unsaturation of the hydrocarbon chain. At room temperature, the saturated fatty acids from 12:0 to 24:0 have a waxy consistency, whereas unsaturated fatty acids of these lengths are oily liquids. This difference in melting points is due to different degrees of packing of the fatty acid molecules. In the fully saturated compounds, free rotation around each carbon–carbon bond gives the hydrocarbon chain great flexibility. These molecules can pack together tightly in nearly crystalline arrays, with atoms all along their lengths in van der Waals contact with the atoms of neighboring molecules. In unsaturated fatty acids, a cis double bond forces a kink in the hydrocarbon chain. This decreases van der Waals contacts: the presence of cis double bonds therefore results in lower melting temperature because they result in less regular and less stable structures. The melting points of different fatty acids differ markedly as shown in this table Differences in melting temperature exist between fatty acids containing the same number of carbon atoms because the preferred conformation of a chain of saturated carbon atoms is a long, straight structure. A trans double bond does not cause a bend in the chain, but a cis double bond causes a bend in the structure, straight molecules can pack together more densely and gives a higher melting temperature. Branching can also affect melting temperature; for example:10-methyl stearic acid melts at only 10°C Longer chains result in higher melting temperatures; increasing numbers of double bonds decreases melting temperature for fatty acids of a given length. Trans Fatty Acids or Trans Fats Trans fatty acids are principally artificial fats but a small amount of TFAs occur naturally in meat and dairy products. Trans fatty acids are formed artificially during the hydrogenation of vegetable oils. In this process, the vegetable oils which are liquid turn to solid. Hydrogenation improves the shelf-life and palatability of oils and thus they are used in food industry. Effects of Trans Fatty Acids in our body: TFAs are more atherogenic than saturated fatty acids. Increasing LDL levels (bad cholesterol) Decreasing HDL (good cholesterol) level Increasing the abnormal clotting of blood. A positive correlation of trans fatty acids with type-2 diabetes and some cancers. Eicosanoids (eikos meaning twenty): Some of the unsaturated fatty acids contain more than one double bond such as linoleic and linolenic acid which required for the biosynthesis of arachidonic acid are the precursor of a class of hormone like molecule known as eicosanoids (prostaglandin, leukotriene and thromboxane). They are paracrine hormone like molecules and differ from endocrine hormones in that they are not transported between tissues in the blood, but act only on cells near the point of their synthesis. Various eicosanoids are produced in different cell types by different synthetic pathways and have different target cells and biological actions in vertebrate animals. Eicosanoids are known to be involved in: 1. Inflammation. 2. Fever and pain associated with injury or disease. 3. Formation of blood clot. 4. Regulation of blood pressure. 5. Gastric acid secretion. Prostaglandins (PG): Prostaglandins are produced in low amounts in most cells in the body, including liver, kidneys, pancreas, heart, lungs, brain, intestine and seminal fluid. The variety of prostaglandins is formed from the polyunsaturated fatty acid (Arachidonic acid) with 20 carbon structure. Prostaglandins are further divided into two groups, ether-soluble prostaglandins (PGE), and phosphate buffer-soluble prostaglandins (PGF). The E-type of PG have a keto group in position 9, whereas the F-type PG have a hydroxyl group in this position. Physiologic effects of prostaglandins:- 1. Some PG regulate blood pressure. 2. Regulate body temperature. 3. Stimulate contraction and relaxation in the smooth muscle of the uterus. 4. Stimulate steroid production by adrenal glands and stimulate the release of insulin from the pancreas. 5. Stimulate the movement of calcium ions from bone. 6. PG have also used to induce abortion. 7. Producing fever, pain and cause inflammation. When tissues are injured, arachidonic acid is converted to PG that produce inflammation and pain in the area. The treatment of pain, fever and Inflammation (such as aspirin NSAIDs) is based on inhibiting the enzyme cyclo-oxygenase that convert arachidonic acid to PG, so decrease pain, inflammation and reduce fever. Mechanism of Aspirin and other Pain Killers action: Prostaglandins induce inflammation, pain, and fever. Aspirin blocks cyclooxygenase which converting arachidonic acid to prostaglandins. The acetyl group on aspirin is hydrolyzed and then bonded to the alcohol group of serine (530) as an ester. This has the effect of blocking the channel in the enzyme and arachidonic can not enter the active site of the enzyme. By inhibiting or blocking this enzyme, the synthesis of prostaglandins is blocked, which in turn relives some of the effects of pain and fever. Consequently thromboxane synthesis is also inhibited, and blood clotting is impaired. This effect has prompted many physicians to recommend a daily dose of 81 mg aspirin for people at risk for heart attack or stroke. It also explains why physicians forbid patients to use aspirin and other anti-inflammatory agents for a week before a planned surgery, aspirin and other NSAIDs may cause excessive bleeding. Aspirin competes with arachidonate for binding to the cyclooxygenase active site. Although arachidonate binds about 10 000 times better than aspirin, once binding of aspirin acetylates a serine (530) residue at the active site to cause irreversible COX inactivation. Although the other non-steroidal anti- inflammatory drugs inhibit COX activity, most of them cause reversible enzyme inhibition by competing with arachidonate for binding. A well-known example of a reversible NSAID is ibuprofen. Cyclooxygenase has two isozymes. Isoenzymes (or isozymes) are multiple form of an enzyme which differ in chemical and physical properties and catalyze the same reaction as an enzyme Aspirin inhibit both COX-1 and COX-2. This explains why aspirin and the other anti- inflammatory agents have undesirable side effects. NSAIDs also interfere with the COX-1 isoform of the enzyme, which is needed for normal physiological function. Their side effects include stomach and duodenal ulceration. Thromboxanes: Were first isolated from thrombocytes (blood platelets). Thromboxane is known to induce platelet aggregation. When a blood vessel is ruptured, the first line of defense is the platelets circulating in the blood, which form an incipient clot. Thromboxane A2 causes other platelets to clump, thereby increasing the size of the blood clot. Thromboxane cause constriction of blood vessels. Leukotrienes: Leukotrienes is the third group of eicosanoids. They were first found in leukocytes (white blood cells). They induce contraction of muscle lining the airways to the lungs. Leukotrienes are potent proiflammatory agents, cause bronchoconstriction. Lipoxins are also produced via the same pathway. Overproduction of leukotrienes causes asthma-like attacks, and leukotriene synthesis is one target of antiasthmatic drugs such as prednisone. 2- Glycerides (Triacylglycerols ): Glycerides are lipid esters that contain the glycerol molecule and fatty acid. Triacylglycerols are not found in membranes, because they are entirely non-polar. Triacylglycerols act as energy storage molecules, especially in adipose tissue they are also found in lipoproteins. Esterification may occur at one, two or all positions of glycerol producing mono- glyceride, diglyceride and triglycerides respectively of different fatty acids, or of three identical fatty acids. The three acyl residues of a fat molecule may differ in their chain length and the presence or absence of double bonds and number of double bonds they contain. This results in a large number of possible combinations of individual fat molecules. Upon oxidation (Beta Oxidation) in the body, unsaturated fatty acids yield less energy than saturated ones of the same size. However, depot fat, which is an energy store, contains a high content of unsaturated fatty acids. This is thought to be so because the fat must be in a liquid state to present a large surface area to enzymes that hydrolyze it. Also, solid fat would render the adipose tissue to be rigid and unyielding during mechanical stress. Glycerophospholipids: Glycerophospholipids are the major component of biological membranes. Glycerophospholipids are composed of two acyl group and a phosphate ester on the third carbon. This makes the glycerophospholipid molecule considerably more polar, because the phosphate group is charged under physiological conditions. Venom of vipers? Some Phospholipids Have Ether-Linked Fatty Acids In some of the glycerophospholipids, one of the two fatty acyl chains is attached to glycerol in ether, rather than, ester linkage. The ether-linked chain may be saturated, as in the alkyl ether lipids (platelet-activating factor), or unsaturated such as plasmalogens that contain a double bond between C1 and C2. Vertebrate heart tissue is uniquely enriched in ether lipids; about half of the heart phospholipids are plasmalogens. Three major classes of plasmalogens have been identified that contain ethanolamine, choline and serine as the head group. The functional significance of ether lipids in these membranes is unknown; but they confer their resistance to the phospholipases that cleave ester-linked fatty acids from membrane lipids is important in some roles. Another ether lipid is platelet-activating factor which released from leukocytes and stimulates platelet aggregation and the release of serotonin (a vasoconstrictor) from platelets, and plays an important role in inflammation and the allergic response. 3- Nonglyceride lipids (sphingolipids): Sphingolipids are derivatives of sphingosine, an 18-carbon amino alcohol. The simplest sphingolipid is ceramide, which is formed from sphingosine bounded in an amide linkage to a fatty acid. Sphingomyelins: its derived from ceramide usually have an additional group attached to the phosphate (choline or ethanolamine). Cerebrosides are ceramide linked by an ether linkage to glucose or galactose. Gangliosides are related to cerebrosides, but it contain three or more sugar residues. Steroids: The steroids are members of a large collection of lipid called the isoprenoids. A major class of simple lipids are terpenes, which are molecules formed from repeating isoprene (2-methyl-1,3-butadiene) units. Terpene is composed of two isoprene molecules; molecules containing one or more terpene units are called terpenes. Examples of terpenes include the diterpene retinol (vitamin A) and the plant compound β-carotene, a tetraterpene that can act as a precursor of retinol. Squalene is a triterpene (30 carbons) compound it acts as a precursor of cholesterol. Steroids are compounds containing the steroid nucleus, which consists of 3 cyclohexane rings and one cyclopentane ring fused together. Cholesterol is a 27- carbon terpene derivative. Most of the cholesterol are incorporated into the lipid layer of plasma membranes, or converted into bile acids. A very small amount of cholesterol is used for biosynthesis of the steroid hormones. Cholesterol is amphipathic, with a polar head group (the hydroxyl group at C3) and a nonpolar hydrocarbon body (the steroid nucleus and the hydrocarbon side chain). Waxes Waxes are esters of long chain (14 to 36 carbon) saturated or unsaturated fatty acids with long chain (16 to 30 carbon) alcohols. Importance of wax : 1- Skin glands of certain vertebrates secrete waxes to protect their hair and skin and keep them lubricated and waterproof. 2- Certain birds have wax secreting glands to prevent their feather from being wet. 3- The leaves of certain tropical plants are also coated with wax to prevent excessive evaporation of water and for protection against parasites. 4- Complex lipids: Lipids which are bonded to other type of molecules. The most important complex lipids are plasma lipoproteins which are responsible for the transport of other lipids in the body. Lipoprotein particles consist of a core of hydrophobic lipids (cholesterol ester or TG) surrounded by amphipathic proteins (containing both hydrophobic and hydrophilic region), phospholipids and cholesterol. Chylomicrons: Carrying dietary TG from the intestine to other tissue. Very low density lipoprotein (VLDL): VLDL is synthesized and released by the liver. VLDL is used to transport triacylglycerol from the liver to other tissues. Low density lipoprotein (LDL): They carry cholesterol to peripheral tissue and helps to regulate cholesterol in those tissues. High levels of LDL cholesterol are associated with elevated risk of heart disease. LDL cholesterol is called the “bad cholesterol”. High density lipoprotein (HDL): They are bound to plasma cholesterol; however, they transport cholesterol from peripheral tissue to the liver. High levels of HDL are associated with reduced risk of heart disease, possibly due to increased cholesterol scavenging by HDL, and therefore lower LDL and total plasma cholesterol levels. HDL cholesterol is called the “good cholesterol”. Rancidity of Fats: The unpleasant odor and taste developed by most natural fats upon ageing is referred to as rancidity. Rancidity may be due to hydrolysis of component glycerides of a fat into free fatty acids and glycerol. If the hydrolysis is incomplete, a mixture of glycerol, monoglycerides and diglycerides with free fatty acids may be produced. Rancidity may also be caused by various oxidative processes. For example, oxidation at the double bonds of unsaturated fatty acyl residues may form peroxides, which then decompose to form aldehydes of bad odor and taste. This process is greatly increased by exposure to light. Addition of minute amounts of antioxidants can prevent the oxidation and rancidity. Biological advantage of Fats Triacylglycerols are ideal molecules for efficient storage of metabolic energy. This is because they are more highly reduced than the other molecules such as carbohydrates or proteins and hence yield significantly more energy upon oxidation. Another advantage is that, fats being nonpolar substances, can be stored in anhydrous form without carrying an extra load of water and occupying less space during storage. Glycogen, on the other hand, binds about twice its weight of water. Triacylglycerols, therefore, provide about six times more energy than an equal weight of hydrated glycogen. Hence, fat appears to be an efficient storage form, but being hydrophobic it does not allow quick mobilization to meet physiological energy requirements. This is the reason that fats are molecules suitable for long-term storage of energy. Glycogen present in human body can meet the metabolic energy requirement only for less than a day, whereas the fat stored in adipocytes can fuel the mammals for days and even weeks. The fat content of normal men and women is about 20% and 26% respectively, which allows them to survive for several days of starvation. In hibernating animals, huge fat accumulated before hibernation serves dual purpose of energy storage and insulation. Fat is also stored in the form of oil in seeds of many plants providing energy and biosynthetic precursors during seed germination. Both adipocytes and germinating seeds contain lipases that catalyze the hydrolysis of stored triacylglycerols, releasing fatty acids for export to sites where they are required as fuel.