Lipid Classification PDF

Classification of Lipids OSAMAH S. AlROUWAB 32  Classification of Lipids I. Simple Lipids  They are called simple because they are formed only from alcohols and Fatty acids.  There are two classes of simple lipids (according to the type of...

Classification of Lipids OSAMAH S. AlROUWAB 32  Classification of Lipids I. Simple Lipids  They are called simple because they are formed only from alcohols and Fatty acids.  There are two classes of simple lipids (according to the type of alcohol): A. acylglycerols and B. waxes. Glycerols Glycerols Glycerols FA FA FA FA OH OH FA FA OH Monoacylglycerols Diacylglycerols Triacylglycerols OSAMAH S. AlROUWAB 33  Classification of Lipids I. Simple Lipids (a) Neutral fats (Triacylglycerol, TG): These are triesters of fatty acids with glycerol.  They are called neutral fat because they carry no charge. Location:  They are stored mainly in the cytoplasm of adipose tissue cells (which are located subcutaneously and around the kidney and other organs).  Body fat is an important source of energy. Each gram of fat gives 9.3 kcal  Human fat is liquid at room temperature and contains high contents of oleic acid. OSAMAH S. AlROUWAB 34  Classification of Lipids I. Simple Lipids Dietary sources of triacylglycerols: - In animals e.g. butter and lard. - In plants e.g. Cotton seed oil, linseed oil, sesame oil, and olive oil. - Marine oils e.g. cod liver oil and shark liver oil. Types of triacylglycerols: - Simple triacylglycerols: similar 3 fatty acids are attached to glycerol. - Mixed triacylglycerols: 3 different fatty acids are attached to glycerol. OSAMAH S. AlROUWAB 35  Classification of Lipids properties of triacylglycerols A. Physical properties: 1. Solubility: All triacylglycerols are insoluble in water, and soluble in fat solvents. 2. Melting point: - Triacylglycerols rich in unsaturated F.A. are liquid at room temperature “Oils”. - Triacylglycerols rich in saturated F.A. are solid at room temperature  “Fats”. 3. Specific gravity: It is less than one. The specific gravity of water is one Therefore, triacylglycerols float on the water’s surface. OSAMAH S. AlROUWAB 36  Classification of Lipids properties of triacylglycerols B. Chemical properties: 1. Hardening (Reduction): Def: Hydrogenation of oils to form solid fat or margarine As: USFA are converted to SEA 2. Hydrolysis of TAG: a. Acid Hydrolysis: Boiling TAG with acids  Glycerol + 3FAs b. Alkaline Hydrolysis (Saponification): Def: Hydrolysis of TAG using alkalis Produces: Glycerol & Soap Soap: Alkaline salt of FA c. Enzymatic Hydrolysis: TAG by lipase enzyme gives glycerol & 3 FAs OSAMAH S. AlROUWAB 37  Classification of Lipids properties of triacylglycerols 3. Rancidity: Def: Development of toxic compound with bad flavor (odor & taste) of fats or oils due to oxidation of USFA. Types: Hydrolytic & oxidative. 1. Hydrolytic Rancidity: Cause: Due to the presence of (H2O) OR Bacteria (Contain lipase enzyme). Lipase causes release of short chain F.As which are volatile. 2. Oxidative Rancidity: Oils are more liable to develop this type of rancidity because they are rich in USFA. Oxidation at USFA → Peroxides, ketones & aldehydes → Bad flavor Prevention of oxidative rancidity Addition of antioxidants such as vitamin E, phenols and quinones OSAMAH S. AlROUWAB 38  Classification of Lipids I. Simple Lipids (b) Waxes are esters of fatty acids with higher monohydroxy aliphatic alcohols. True waxes(Bee wax) are esters of higher fatty acids with higher straight-chain alcohols. Cholesterol esters are esters of fatty acid with cholesterol  Lanolin (in hair). Vit A and Vit D esters are palmitic or stearic acids esters of Vit A (Retinol) or Vit D respectively. OSAMAH S. AlROUWAB 39  Classification of Lipids Properties of waxes: 1. They have the same physical properties as fat. 2. They give a negative Acrolein test because they contain no glycerol. 3. They are not digested by lipase enzymes. Thus they are not utilized. 4. They are solids at room temperature. OSAMAH S. AlROUWAB 40 OSAMAH S. AlROUWAB 41 OSAMAH S. ALROUWAB 42  PHOSPHOLIPIDS: CHEMISTRY AND FUNCTIONS Definition: Phospholipids are compound lipids, they contain in addition to fatty acids and glycerol/or other alcohol, a phosphoric acid residue, nitrogen-containing base, and other substituents. phosphate fatty acids Alchol fatty acids Choline Serine nitrogenous Ethanolamine base Inositol OSAMAH S. ALROUWAB 43  PHOSPHOLIPIDS: CHEMISTRY AND FUNCTIONS Classification: Classification given by Celmer and Carter is used, which is based on the type of alcohol present in the phospholipids. Thus they are classified mainly into the following three groups: 1- Glycerophosphatides glycerol is the alcohol group (glycerophospholipids) 2- Sphingophospholipids Sphingosine (sphingol) is the (Sphingomyelins) alcohol group OSAMAH S. ALROUWAB 44  PHOSPHOLIPIDS: CHEMISTRY AND FUNCTIONS 1- Glycerophosphatides Without nitrogenous base With nitrogenous base 1- Phosphatidylcholine (Lecithin ) 7- diphosphatidylglycerol (Cardiolipins) 2- phosphatidylethanolamines (Cephalins) 8- Phosphatidylinositol 3- Phosphatidylserine 4- Lysophosphatides 5- Plasmalogen 6- Platelet Activating Factor OSAMAH S. ALROUWAB 45  PHOSPHOLIPIDS: CHEMISTRY AND FUNCTIONS 1- Glycerophosphatides - Phospholipids containing glycerol as alcohol SFA - They are derivatives of phosphatidic acid. 1. Phosphatidic acid: USFA Diacylglycerol phosphate P Formed during synthesis of TAG & phospholipid FA at position 1 is SFA & at position 2 USFA OSAMAH S. ALROUWAB 46  PHOSPHOLIPIDS: CHEMISTRY AND FUNCTIONS 1- PHOSPHATIDYL CHOLINE (LECITHIN)  Formed of phosphatidic acid + Choline  It is widely distributed in animals in the SFA liver, brain, nerve tissues, sperm, and egg USFA yolk, having both metabolic and structural functions. In plants, particularly abundant P Choline in seeds and sprouts. Lecithin is “generally recognized as safe”  On hydrolysis, lecithin yields: (GRAS) by the United States Food and Drug (a) glycerol, (b) fatty acids, (c) phosphoric acid and Administration (FDA). (d) nitrogenous base choline.  Depending on the position of the phosphoric acid-choline complex, on α or β carbon, α-lecithin and β-lecithin OSAMAH S. ALROUWAB 47  PHOSPHOLIPIDS: CHEMISTRY AND FUNCTIONS 1- PHOSPHATIDYL CHOLINE (LECITHIN) Functions:  Enters in the structure of the cell membrane.  Acts as a lipotropic factor (helps in fat breakdown during metabolism)  prevents fatty liver.  Lecithin acts as the body store of Choline. Choline is important for: i- Nerve transmission. II- Transmethylation acts as a methyl donor  Dipalmityl lecithin (i.e. lecithin which contains 2 palmitic acid residues) Act as a surfactant in lung Dipalmityl lecithin is continuously secreted by the lung cells in the alveolar wall, forming a monolayer over the watery surface of the alveolus and so lowering the surface tension  expiration and inspiration OSAMAH S. ALROUWAB 48 PHOSPHOLIPIDS: CHEMISTRY AND FUNCTIONS OSAMAH S. ALROUWAB 49  PHOSPHOLIPIDS: CHEMISTRY AND FUNCTIONS 1- PHOSPHATIDYL CHOLINE (LECITHIN) Respiratory distress syndrome (hyaline membrane disease) In premature babies, lungs do not secrete enough surfactant. This leads to lung collapse and death from respiratory failure. Treatment of this case needs putting the premature babies in an incubator and administration of surfactant locally in the lung. OSAMAH S. ALROUWAB 50  PHOSPHOLIPIDS: CHEMISTRY AND FUNCTIONS 2- Phosphatidyl Ethanolamine (Cephalins)  Cephalins are structurally identical to Lecithins, with the exception that the base ethanolamine replaces choline.  Both α and β cephalins are known. They occur with lecithin, particularly rich in brain and nervous tissues 3- Phosphatidyl Serine  A cephalin a phospholipid contains amino acid serine in place of ethanolamine  Found in brain and nervous tissues and a small amount in other tissues. Also Found in the blood. OSAMAH S. ALROUWAB 51  PHOSPHOLIPIDS: CHEMISTRY AND FUNCTIONS 4- Lysophosphatides  These are phosphoglycerides containing only one acyl radical in α position, e.g. lysolecithin.  Formation: They can be formed in two ways: By the action of phospholipase enzyme Alternatively, it can also be formed by the interaction of lecithin and cholesterol in the presence of the enzyme Lecithin cholesterol acyl transferase (LCAT). Cholesterol esters are transported to the liver  excreted with bile  prevent atherosclerosis Lecithin + Cholesterol Cholesterol ester + lysolecithin OSAMAH S. ALROUWAB 52 PHOSPHOLIPIDS: CHEMISTRY AND FUNCTIONS OSAMAH S. ALROUWAB 53 PHOSPHOLIPIDS: CHEMISTRY AND FUNCTIONS OSAMAH S. ALROUWAB 54  PHOSPHOLIPIDS: CHEMISTRY AND FUNCTIONS 5- Plasmalogens  The plasmalogens make up an appreciable amount, about 10 percent of total phospholipids of brain and nervous tissue, muscle, and mitochondria. Ether Bond  Same structure as lecithin but SFA at position 1 is replaced by USF Alcohol unsaturated fatty alcohol USFA Ether Bond 6- Platelet Activating Factor P Choline  Same structure as Plasmalogens but unsaturated fatty alcohol at SF Alcohol position 1 is replaced by saturated fatty alcohol  unsaturated fatty acid at position 2 is replaced by Acetic acid Acetic acid P Choline OSAMAH S. ALROUWAB 55  PHOSPHOLIPIDS: CHEMISTRY AND FUNCTIONS 7- Diphosphatidylglycerol (Cardiolipins)  A phospholipid found in mitochondria (inner membrane) and bacterial wall.  Chemically, it is diphosphatidyl glycerol  without a nitrogenous base  the only phosphoglyceride that possesses antigenic properties. OSAMAH S. ALROUWAB 56  PHOSPHOLIPIDS: CHEMISTRY AND FUNCTIONS 8- Phosphatidylinositol  Like lecithin but it contains inositol instead of choline  Present in cell membrane. It acts as a precursor of the second messenger (inositol triphosphate), mediating hormonal action OSAMAH S. ALROUWAB 57  PHOSPHOLIPIDS: CHEMISTRY AND FUNCTIONS 2- Sphingophospholipids (Sphingomyelins)  Found in large quantities in brain and nervous tissues, and very small amounts in other tissues.  It does not contain glycerol. In place of glycerol, it contains an unsaturated amino alcohol called ‘sphingosine’ (sphingol).  A sphingosine molecule in which a fatty acyl group is substituted on the –NH2 group is called as ceramide  When choline is split off from sphingomyelin, ceramide phosphate is left. Sphingomyelinase is the enzyme which hydrolyses sphingomyelin to form ceramide and phosphorylcholine OSAMAH S. ALROUWAB 58 OSAMAH S. ALROUWAB 59  PHOSPHOLIPIDS: CHEMISTRY AND FUNCTIONS CLINICAL ASPECT OF SPHINGOMYELINS NIEMANN-PICK DISEASE  Large accumulations of sphingomyelins may occur in the brain, liver, and spleen of some persons suffering from Niemann-Pick disease.  It is an inherited disorder of sphingomyelin metabolism in which sphingomyelin is not degraded, as a result, sphingomyelin accumulates. It is a lipid-storage disease (lipidoses).  Enzyme defect: Deficiency of the enzyme sphingomyelinase, a lysosomal enzyme.  Prognosis: Usually fatal. Over 80 % of infants die within 2 years. OSAMAH S. ALROUWAB 60  GLYCOLIPIDS: CHEMISTRY AND FUNCTIONS  Formed of ceramide (Sphingosine + FA) attached to carbohydrates.  Includes cerebrosides, Gangliosides and Sulfolipids 1. CEREBROSIDES (GLYCOSPHINGOSIDES)  Cerebrosides occur in large amounts in the white matter of the brain and in the myelin sheaths of nerves.  They are not found in the embryonic brain.  There is no glycerol, no phosphoric acid, and no nitrogenous base. Thus, a cerebroside, on hydrolysis, yields: A sugar, usually galactose, but sometimes glucose A high molecular weight fatty acid and The alcohol, sphingosine, or dihydrosphingosine. OSAMAH S. ALROUWAB 61  GLYCOLIPIDS: CHEMISTRY AND FUNCTIONS  Types of cerebrosides: cerebrosides are differentiated by the kinds of fatty acids in the molecule. Four types of cerebrosides have been isolated and their fatty acids have been identified. They are: 1- Kerasin: Contains normal lignoceric acid as fatty acid. 2- Cerebron (Phrenosin): Contains hydroxy lignoceric acid, also called cerebronic acid. 3- Nervon: Contains an unsaturated fatty acid called nervonic acid 4- Oxynervon: Contains hydroxy derivative of nervonic acid. OSAMAH S. ALROUWAB 62  GLYCOLIPIDS: CHEMISTRY AND FUNCTIONS CLINICAL ASPECT OF CEREBROSIDES Gaucher’s Disease An inherited disorder of cerebrosides metabolism (lipidosis).  Enzyme defect: Deficiency of the enzyme β-Glucocerebrosidase, a lysosomal enzyme. Normally this enzyme hydrolyses glucocerebrosides to form ceramide and glucose.  In the absence of the enzyme, the cerebrosides cannot be degraded in the body, as a result, large amounts of glucocerebrosides, usually kerasin accumulate in liver, spleen, bone marrow, and brain cells.  Biochemically, there is characteristically elevation in serum acid phosphatase level. Clinical features: Adults as well as infants are affected. (a) In infancy and childhood: Fairly acute onset, with rapid course and death in several years. (b) In adults: Progressive enlargement of the spleen (splenomegaly), bone pain, anemia, leucopenia and thrombocytopenia, a tendency to get secondary infections and bleeding tendency. OSAMAH S. ALROUWAB 63 GLYCOLIPIDS: CHEMISTRY AND FUNCTIONS CLINICAL ASPECT OF CEREBROSIDES Gaucher’s Disease OSAMAH S. ALROUWAB 64  GLYCOLIPIDS: CHEMISTRY AND FUNCTIONS 2. GANGLIOSIDES  Klenk, in 1942, isolated from beef brain, a new class of carbohydrate-rich glycolipids which he called gangliosides.  Gangliosides have been isolated from ganglion cells, neuronal bodies, dendrites, spleen, and RBC. The highest concentrations are found in the gray matter of the brain.  Gangliosides are the most complex of the glycosphingolipids. OSAMAH S. ALROUWAB 65  GLYCOLIPIDS: CHEMISTRY AND FUNCTIONS Structure: Although the exact structures of the gangliosides are not established. On hydrolysis, gangliosides yield the following: A long chain FA (usually C18 to C24). Alcohol-sphingosine. A carbohydrate moiety which usually contains: – Glucose and/or galactose, – One molecule of N-acetyl galactosamine, and – At least one molecule of N-acetyl neuraminic acid (NANA) (also called ‘sialic acid’). Brain gangliosides are known to be complex and mono-, di-, trisialogangliosides containing 1 to 3 sialic acid residues. OSAMAH S. ALROUWAB 66  GLYCOLIPIDS: CHEMISTRY AND FUNCTIONS Types of gangliosides: Over 30 types of gangliosides have been isolated from brain tissue. Four important types are: GM-1, GM-2, GM-3 and GD-3. Their structures are OSAMAH S. ALROUWAB 67  GLYCOLIPIDS: CHEMISTRY AND FUNCTIONS Biomedical Importance Types of gangliosides: Over 30 types of gangliosides have been isolated from brain tissue. Four important types are: GM-1, GM-2, GM-3 and GD-3. Their structures are  Gangliosides are the main components of ‘membranes’.  The sugar units and sialic acid sections of the molecule are “water-soluble” (i.e. “hydrophilic”) and –very charged, whereas the ceramide portion is ‘lipid soluble’ (i.e. “hydrophobic”).  The hydrophobic sections appear to be embedded in the membrane lipids, whereas  the hydrophilic sections, with their charged units, protrude externally toward the medium.  The gangliosides, therefore, can serve as specific membrane binding sites (receptor sites) for circulating hormones and thereby influence various biochemical processes in the cell. OSAMAH S. ALROUWAB 68  GLYCOLIPIDS: CHEMISTRY AND FUNCTIONS CLINICAL ASPECT (a) Tay-Sachs Disease (GM2 Gangliosidosis)  Accumulation of gangliosides in brain and nervous tissues takes place.  The affected ganglioside is GM2.  The Enzyme deficiency is hexosaminidase A.  Subsequently, the other components are hydrolyzed by other specific enzymes. This rare inherited disorder is associated with: Progressive development of idiocy and blindness in infants soon after birth. This is due to widespread injury to ganglion cells in the brain (cerebral cortex) and retina. A cherry-red spot about the macula caused by the destruction of retinal ganglion cells. There may be seizures and The prognosis is bad, usually death follows OSAMAH S. ALROUWAB 69 GLYCOLIPIDS: CHEMISTRY AND FUNCTIONS CLINICAL ASPECT OSAMAH S. ALROUWAB 70  GLYCOLIPIDS: CHEMISTRY AND FUNCTIONS CLINICAL ASPECT (b) GM1 Gangliosidosis  It is due to a deficiency of the enzyme β-galactosidase.  leading to the accumulation of GM1 gangliosides, glycoproteins, and the mucopolysaccharide karatan sulphate. OSAMAH S. ALROUWAB 71  GLYCOLIPIDS: CHEMISTRY AND FUNCTIONS 3. SULPHOLIPIDS  Lipid material containing sulfur has long been known to be present in various tissues and has been found in the liver, kidney, testes, brains, and certain tumors.  Most abundant in the white matter of the brain. CLINICAL ASPECT 1. Metachromatic Leucodystrophy (MLD):  It is an inherited disorder in which sulfatide accumulates in various tissues.  Sulphatide is formed from ‘galactocerebroside’ through the esterification of OH group on C3 of galactose with H2SO4.  The ratio of cerebroside: to sulphatide in the brain normally is 3:1.  In this disorder, it is altered to 1:4.  Enzyme deficiency: Deficiency of enzyme sulphatase called as Aryl sulfatase A. OSAMAH S. ALROUWAB 72  GLYCOLIPIDS: CHEMISTRY AND FUNCTIONS Types: Two clinical types are seen. (a) Late infantile type: Usually manifests before 3 years, gross involvement of CNS: Defects in locomotion, weakness, ataxia, hypotonus, and paralysis Difficulties in speech There may be optic atrophy. (b) Adult type: Initially associated with psychiatric manifestations but subsequently progressive dementia. OSAMAH S. ALROUWAB 73  GLYCOLIPIDS: CHEMISTRY AND FUNCTIONS 2. Fabry’s disease: An inherited disorder, a lipid storage disease (lipidosis). Inheritance: X-linked dominant, full symptoms only in males. Enzyme deficiency: α-galactosidase. The enzyme is found normally in the liver, spleen, kidney, brain, and small intestine. Nature of lipid that accumulates ceramide trihexoside (globotriosyl ceramide) Clinical manifestations: -Skin rash (reddish purple), -Lipid accumulates in the endothelial lining of blood vessels, -Progressive renal failure–due to extensive deposition of lipids in glomeruli. -Eye involvement: Corneal opacities, cataracts, OSAMAH S. ALROUWAB 74  GLYCOLIPIDS: CHEMISTRY AND FUNCTIONS 3. Krabbe’s Disease An inherited disorder of lipid metabolism, a lipid storage disease (lipidosis) Enzyme deficiency: Galactocerebrosidase (α-galactosidase). The enzyme normally catalyzes the hydrolysis of galactocerebrosides and it splits the linkage between ceramide and galactose OSAMAH S. ALROUWAB 75  GLYCOLIPIDS: CHEMISTRY AND FUNCTIONS 3. Krabbe’s Disease Nature of lipid accumulating: Galactosyl ceramide Clinical manifestations: – Severe mental retardation in infants – Total absence of myelin in central nervous system – Globoid bodies found in white matter of brain. Prognosis: Fatal. OSAMAH S. ALROUWAB 76