Lipid chemistry


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Chemistry of fatty acids, cholesterol, simple and compound lipids

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Lipid chemistry

  1. 1. Biochemistry for medics Biochemistry for medics 6/29/2012 1
  2. 2. The lipids are a heterogeneous group ofcompounds, including fats, oils, steroids, waxes,and related compounds, that are related more bytheir physical than by their chemical properties.They have the common property of being(1) relatively insoluble in water and (2) solublein nonpolar solvents such as ether andchloroform. Biochemistry for medics 6/29/2012 2
  3. 3.  Storage form of energy Important dietary components because of their high energy value and also because of the fat-soluble vitamins and the essential fatty acids contained in the fat of natural foods. Structural components of biomembranes Serve as thermal insulators in the subcutaneous tissues and around certain organs Nonpolar lipids act as electrical insulators, allowing rapid propagation of depolarization waves along myelinated nerves Biochemistry for medics 6/29/2012 3
  4. 4.  Provide shape and contour to the body Act as metabolic regulators Combinations of lipid and protein (lipoproteins) are important cellular constituents, occurring both in the cell membrane and in the mitochondria, and serving also as the means of transporting lipids in the blood. Biochemistry for medics 6/29/2012 4
  5. 5. Following diseases are associated withabnormal chemistry or metabolism of lipids-ObesityAtherosclerosisDiabetes MellitusHyperlipoproteinemiaFatty liverLipid storage diseases Biochemistry for medics 6/29/2012 5
  6. 6. Simple lipids: Esters of fatty acids with variousalcohols.a. Fats: Esters of fatty acids with glycerol. Oils arefats in the liquid state.b. Waxes: Esters of fatty acids with highermolecular weight monohydric alcohols. Biochemistry for medics 6/29/2012 6
  7. 7. 2. Complex lipids: Esters of fatty acids containinggroups in addition to an alcohol and a fatty acid. a. Phospholipids: Lipids containing, in addition to fattyacids and an alcohol, a phosphoric acid residue. Theyfrequently have nitrogen-containing bases and othersubstituents, eg, in glycerophospholipids the alcohol isglycerol and in sphingophospholipids the alcohol issphingosine.b. Glycolipids (glycosphingolipids): Lipids containing afatty acid, sphingosine, and carbohydrate.c. Other complex lipids: Lipids such as sulfolipids andaminolipids. Lipoproteins may also be placed in thiscategory. Biochemistry for medics 6/29/2012 7
  8. 8. 3) Precursor and derived lipids: These include- fatty acids glycerol steroids other alcohols fatty aldehyde ketone bodies hydrocarbons, lipid-soluble vitamins, and hormones. Biochemistry for medics 6/29/2012 8
  9. 9. Fatty acids are aliphatic carboxylic acidsHave the general formula R-(CH2)n-COOHThey occur mainly as esters in natural fatsand oils but do occur in the unesterified formas free fatty acids, a transport form found inthe plasma.Fatty acids that occur in natural fats areusually straight-chain derivatives containingan even number of carbon atoms.The chain may be saturated (containing nodouble bonds) or unsaturated (containingone or more double bonds). Biochemistry for medics 6/29/2012 9
  10. 10. Fatty acids can be classified in many ways-1) According to nature of the hydrophobicchain-a) Saturatedb) Unsaturatedc) Branched chain fatty acidsd) Substituted Fatty acidsSaturated fatty acids do not contain doublebonds, while unsaturated fatty acids containdouble bonds Biochemistry for medics 6/29/2012 10
  11. 11. Saturated fatty acids may be envisaged asbased on acetic acid (CH3 —COOH) as thefirst member of the series in which —CH2 —is progressively added between the terminalCH3 — and —COOH groups.Fatty acids in biological systems usuallycontain an even number of carbon atoms,typically between 14 and 24. The 16- and18-carbon fatty acids are most common.The hydrocarbon chain is almost invariablyunbranched in animal fatty acids. A fewbranched-chain fatty acids have also beenisolated from both plant and animal sources. Biochemistry for medics 6/29/2012 11
  12. 12. Number of C Common Name Systemic Name Formulaatoms2 Acetic acid Ethanoic acid CH3COOH4 Butyric acid Butanoic acid CH3(CH2)2COOH6 Caproic acid Hexanoic acid CH3(CH2)4COOH8 Caprylic acid Octanoic acid CH3(CH2)6COOH10 Capric acid Decanoic acid CH3(CH2)8COOH12 Lauric acid Dodecanoic acid CH3(CH2)10COOH14 Myristic acid Tetradecanoic CH3(CH2)12COOH acid16 Palmitic acid Hexadecanoic CH3(CH2)14COOH acid18 Stearic acid Octadecanoic CH3(CH2)16COOH acid20 Arachidic acid Eicosanoic acid CH3(CH2)18COOH22 Behenic acid Docosanoicfor medics CH3(CH2)20COOH Biochemistry acid 6/29/2012 12
  13. 13. Unsaturated fatty acids may further be divided asfollows-(1) Monounsaturated (monoethenoid, monoenoic) acids,containing one double bond.(2) Polyunsaturated (polyethenoid, polyenoic) acids,containing two or more double bonds.The configuration of the double bonds in mostunsaturated fatty acids is cis.The double bonds in polyunsaturated fatty acids areseparated by at least one methylene group. Biochemistry for medics 6/29/2012 13
  14. 14. Biochemistry for medics 6/29/2012 14
  15. 15. The systematic name for a fatty acid is derivedfrom the name of its parent hydrocarbon by thesubstitution of oicfor the final e.For example, the C18 saturated fatty acid iscalled octadecanoic acid because the parenthydrocarbon is octadecane.A C18 fatty acid with one double bond is calledoctadecenoic acid; with two double bonds,octadecadienoic acid; and with three doublebonds, octadecatrienoic acid.The notation 18:0 denotes a C18 fatty acid withno double bonds, whereas 18:2 signifies that thereare two double bonds. Biochemistry for medics 6/29/2012 15
  16. 16. Carbon atoms are numbered from thecarboxyl carbon (carbon No. 1). The carbonatoms adjacent to the carboxyl carbon (Nos.2, 3, and 4) are also known as the α ,β , andcarbons, respectively, and the terminalmethyl carbon is known as theω or n-carbon.The position of a double bond is representedby the symbol ∆followed by a, ∆ 9 indicates a double bond betweencarbons 9 and 10 of the fatty acid; Biochemistry for medics 6/29/2012 16
  17. 17. Alternatively, the position of a double bond can bedenoted by counting from the distal end, with the ω-carbon atom (the methyl carbon) as number 1. ω9 indicates a double bond on the ninth carbon countingfrom the ω-carbon.In animals, additional double bonds are introduced onlybetween the existing double bond (eg, 9, 6, or 3) and thecarboxyl carbon, leading to three series of fatty acidsknown as the ω9, ω6, and ω3 families, respectively. Biochemistry for medics 6/29/2012 17
  18. 18. S.No. Number of C Family Common Systemic atoms, Name Name number and location of double bonds[A] Monoenoic acids (one double bond)1. 16:1;9 ω7 Palmitoleic cis-9- acid Hexadecenoic2. 18:1;9 ω9 Oleic Acid cis-9- Octadecenoic3. 18:1;9 ω9 Elaidic acid trans 9- Octadecanoic[B] Dienoic acids (two double bonds)1. 18:2;9,12 ω6 Linoleic acid all-cis-9,12- Biochemistry for medics Octadecadieno 6/29/2012 18
  19. 19. S.No. Number of C Family Common Systemic atoms, Name Name number and location of double bonds[c] Trienoic acids (three double bonds)1. 18:3;6,9,12 ω6 Y- Linolenic all-cis- acid 6,9,12- Octadecatrien oic2. 18:3;9,12,15 ω3 α-Linolenic all-cis- 9,12,15Octad ecatrienoic[D] Tetraenoic acid(Four double bonds) 20:4;5,8,11, ω6 Arachidonic Biochemistry for medics all-cis- 6/29/2012 19
  20. 20. S.No. Number of C Family Common Systemic atoms, Name Name number and location of double bonds[E] Pentaenoic acids (Five double bonds)1. 20:5;5,8,11,1 ω3 Timnodonic all-cis- 4,17 acid 5,8,11,14,17- Eicosapenta enoic[F] Hexaenoic acid(Four double bonds) 22:6;4,7,10,1 ω3 Cervonic acid all-cis- 3,16,19 4,7,10,13,16, Biochemistry for medics 6/29/2012 20 19-
  21. 21. Biochemistry for medics 6/29/2012 21
  22. 22.  Depending upon the orientation of the radicals around the axis of the double bond- Cis- If the radicals are on the same side of the double bond Trans- If the radicals are on the opposite side Oleic acid and Elaidic acid have the same formula but Oleic acid is cis while Elaidic acid is Trans Fatty acid Biochemistry for medics 6/29/2012 22
  23. 23. The hydrocarbon chains in saturatedfatty acids are, fairly straight and canpack closely together, making thesefats solid at room temperature.Oils, mostly from plant sources, havesome double bonds between some ofthe carbons in the hydrocarbon tail,causing bends or ―kinks‖ in the shapeof the molecules.Increase in the number of cis doublebonds in a fatty acid leads to a varietyof possible spatial configurations ofthe molecule—eg, Arachidonic acid,with four cis double bonds, has "kinks"or a U shape. Biochemistry for medics 6/29/2012 23
  24. 24.  Because of the kinks in the hydrocarbon tails, unsaturated fats can‘t pack as closely together, making them liquid at room temperature. The membrane lipids, which must be fluid at all environmental temperatures, are more unsaturated than storage lipids. Lipids in tissues that are subject to cooling, eg, in hibernators or in the extremities of animals, are more unsaturated. At higher temperatures, some bonds rotate, causing chain shortening, which explains why biomembranes become thinner with increases in temperature. The carbon chains of saturated fatty acids form a zigzag pattern when extended, as at low temperatures. Biochemistry for medics 6/29/2012 24
  25. 25.  Trans fatty acids are present in certain foods, arising as a by-product of the saturation of fatty acids during hydrogenation, or "hardening," of natural oils in the manufacture of margarine. An additional small contribution comes from the ingestion of ruminant fat that contains trans fatty acids arising from the action of microorganisms in the rumen. Naturally-occurring unsaturated vegetable oils have almost all cis bonds, but using oil for frying causes some of the cis bonds to convert to trans bonds. Biochemistry for medics 6/29/2012 25
  26. 26. c)Branched Chain Fatty acids Phytanic acid present in butterSebum also contains branched chain fattyacidsThere may be even or odd chain fatty acids.Even chain fatty acids are predominantlypresent.d) Cyclic fatty acids- Chaulmoogric acid and Hydnocarpic acide) Substituted fatty acids Cerebronic acid- OH fatty acid Biochemistry for medics 6/29/2012 26
  27. 27.  Short chain-with 2-6 carbon atoms Medium chain- with 8-14 carbon atoms Long chain- with 16-18 carbon atoms Very long chain fatty acids- with 20 or more carbon atoms Biochemistry for medics 6/29/2012 27
  28. 28. 1-Fatty acids are the building blocks of dietaryfats. The human body stores such fats in theform of triglycerides.2)- Fatty acids are also required for theformation of membrane lipids such asphospholipids and glycolipids.3) -They are required for the esterificaton ofcholesterol to form cholesteryl esters.4) They act as fuel molecules and are oxidized toproduce energy. Biochemistry for medics 6/29/2012 28
  29. 29. Polyunsaturated fatty acids such as Linoleic andLinolenic acids are essential for normal lifefunctions. They are therefore characterized asessential fatty acids.Arachidonic acid is considered as semi essentialfatty acid since it can be synthesized fromLinoleic acid .Essential polyunsaturated fatty acids can beclassified as belonging to one of two "families",the omega-6 family or the omega-3 family.Fatty acids belonging to these two familiesdiffer not only in their chemistry, but also intheir natural occurrence and biological functions. Biochemistry for medics 6/29/2012 29
  30. 30. Components of cell membranes, structural elements ofgonads and mitochondrial membraneRequired for brain growth and developmentPrecursors of EicosanoidsPlay important role in visionThey have a cardio protective role- Lower serumcholesterol and increase HDL levelsPrevent fatty liver formationDeficiencies of essential polyunsaturated fatty acids maycause a wide variety of symptoms, including retardedgrowth in children, reduced fertility and pathologicchanges in the skin. Biochemistry for medics 6/29/2012 30
  31. 31. Also called ‗Glycerin‘.Trihydric alcohol as it contains threehydroxyl groupsCan be obtained from diet, from lipolysis offats in adipose tissue and from glycolysis. Can be utilized for the synthesis oftriacylglycerols, phospholipids, glucose orcan be oxidized to provide energy Used as a solvent in the preparation ofdrugs and cosmeticsNitroglycerine is used as a vasodilator Biochemistry for medics 6/29/2012 31
  32. 32. To number the carbon atoms of glycerolunambiguously, the -sn (stereochemicalnumbering) system is used.Carbons 1 and 3 of glycerol are not identicalwhen viewed in three dimensions.Enzymes readily distinguish between themand are nearly always specific for one or theother carbon; eg, glycerol is alwaysphosphorylated on sn-3 by glycerol kinase togive glycerol 3-phosphate and not glycerol 1-phosphate. Biochemistry for medics 6/29/2012 32
  33. 33. Most important sterol inhuman body Molecular formula-C27H45OHPossesses a cyclo pentanoperhydrophenatherene ringnucleusHas an -OH group at C3 A double bond between C5and C6 Two- CH3 groups at C10and C13An eight carbon side chainattached to C17 Biochemistry for medics 6/29/2012 33
  34. 34. Cholesterol occurs both as free form or in ester form In cholesteryl ester, the hydroxyl group on position 3 is esterified witha long-chain fatty acid.Cholesterol esters are formed by the transfer of acyl group by Acyltransferases-(LCAT and ACAT)In plasma, both forms are transported in lipoproteinsPlasma low-density lipoprotein (LDL) is the vehicle of uptake ofcholesterol and cholesteryl ester into many tissues.Free cholesterol is removed from tissues by plasma high-densitylipoprotein (HDL) and transported to the liver, where it is eliminatedfrom the body either unchanged or after conversion to bile acids in theprocess known as reverse cholesterol transportA sum total of free and ester cholesterol in serum is called serum totalcholesterol Biochemistry for medics 6/29/2012 34
  35. 35. Cholesterol is widely distributed in all cells of thebody but particularly in nervous tissue.It is a major constituent of the plasma membraneand of plasma lipoproteins.It is synthesized in many tissues from acetyl-CoAand is the precursor of all other steroids in the body,including corticosteroids, sex hormones, bile acids,and vitamin D.Cholesterol is a major constituent of gallstones.Its chief role in pathologic processes is as a factorin the genesis of atherosclerosis of vital arteries,causing cerebrovascular, coronary, and peripheralvascular disease. Biochemistry for medics 6/29/2012 35
  36. 36. Normal level of serum total cholesterolranges between 150-220 mg/dL Physiological variations-Low at the time of birth, increases withadvancing age.The level is increased during pregnancyPathological Variations-a) Low cholesterol (Hypocholesterolemia)-Thyrotoxicosis, anemia, hemolytic jaundice,wasting diseases and malabsorptionsyndrome. Biochemistry for medics 6/29/2012 36
  37. 37. B) Hypercholesterolemia- Nephrotic syndromeDiabetes MellitusObstructive JaundiceMyxoedemaXanthomatous biliary cirrhosisHypopituitarismFamilial HypercholesterolemiaIdiopathic Biochemistry for medics 6/29/2012 37
  38. 38. 7- dehydrocholesterol- also called asProvitamin D3 (Precursor of vitamin D)Ergo sterol-plant sterol (First isolated fromErgot- Fungus of Rye)Stigmasterol and Sitosterol- Plant sterolsCoprosterol (Coprostanol)- Reducedproducts of cholesterol- found in fecesOther steroids- Bile acids, adrenocorticalhormones, gonadal hormones, D vitamins andCardiac glycosides. Biochemistry for medics 6/29/2012 38
  39. 39.  Neutral fats or Triacyl Glycerides-The triacylglycerols are esters of thetrihydric alcohol, glycerol and fatty acids.Mono- and Diacylglycerol, wherein one ortwo fatty acids are esterified with glycerol,are also found in the tissues. Naturally occurring fats and oils aremixtures of triglycerides.If all the OH groups are esterified tosame fatty acids- It is Simple TriglycerideIf different fatty acids are esterified- it isknown as Mixed triglyceride.Polyunsaturated fatty acid is esterified at2nd position. Biochemistry for medics 6/29/2012 39
  40. 40. Colourless, odourless and tastelessInsoluble in waterSpecific gravity is less than 1.0,consequently all fats float in waterOils are liquids at 200C, they contain higherproportion of Unsaturated fatty acidsFats are solid at room temperature andcontain saturated long chain fatty acidsTriglycerides are the storage form of energyin adipose tissueTriglycerides in the body are hydrolyzed byLipases Biochemistry for medics 6/29/2012 40
  41. 41.  Lipases are enzymes which catalyzehydrolysis of triglycerides yielding fatty acidsand glycerol Lipases are present in following places-Lingual Lipase-In salivaGastric lipase- in gastric juicePancreatic lipase –in pancreatic juiceIntestinal lipase- in intestinal epithelial cellsHormone sensitive lipase – in adipose tissue Biochemistry for medics 6/29/2012 41
  42. 42. Saponification-When the triglycerides are hydrolyzed byalkali the process is known as Saponification.Rancidity-Fats and oils have a tendency to become rancid.Rancidity refers to the appearance of unpleasant taste andsmell of fats.Hydrolytic rancidity is due to partial hydrolysis oftriglycerides due to traces of lipases present in the given fatOxidative rancidity is due to partial oxidation ofunsaturated fatty acids with the resultant formation ofepoxides and peroxides by free radicals.Preserving the fats with antioxidants can prevent rancidity Biochemistry for medics 6/29/2012 42
  43. 43. They are esters of higher fatty acids with highermono hydroxy aliphatic alcohols(e.g. Cetyl alcohol) Have very long straight chain of 60-100 carbonatomsThey can take up water without getting dissolved initUsed as bases for the preparation of cosmetics,ointments, polishes, lubricants and candles. In nature, they are found on the surface of plantsand insects. Biochemistry for medics 6/29/2012 43
  44. 44. Lipid index Details SignificanceSaponification number Number of mg of KOH Indicates molecular required to saponify the weight and is inversely free and combined fatty proportional to it. acids in 1G. of a given fatIodine number Number of grams of It is a measure of degree iodine absorbed by 100 of unsaturation of a fat gm of fatAcid number Number of mg of KOH Indicates the degree of required to neutralize the rancidity of a fat fatty acids in a gram of a fat Biochemistry for medics 6/29/2012 44
  45. 45. Lipid index Details SignificancePolenske number Number of ml of 0.1 Indicates the presence of normal KOH required to non volatile fatty acids in neutralize the insoluble a given fat fatty acids from 5 gram of fatReichert-Meissl Number Number of ml of 0.1 N Measures the amount of alkali required to volatile soluble fatty neutralize the soluble acids. fatty acids distilled from 5 G of fatAcetyl Number Number of mg of KOH Measures the number of required to neutralize the –OH groups present in a acetic acid obtained by fatty acid saponification of 1G.of fat after it has been acetylated. Biochemistry for medics 6/29/2012 45
  46. 46. a)Phospholipids-Contain in addition to fatty acids andglycerol/or other alcohol, a phosphoric acidresidue, nitrogen containing base and othersubstituents.Phospholipids may be regarded asderivatives of phosphatidic acid , in whichthe phosphate is esterified with the —OH of asuitable alcohol.They are amphipathic molecules containinga polar head and a hydrophobic portion Biochemistry for medics 6/29/2012 46
  47. 47. Biochemistry for medics 6/29/2012 47
  48. 48. Based on nature of alcohol-1)Glycerophospholipids- Glycerol is the alcohol group.Examples-o Phosphatidyl cholineo Phosphatidyl ethanolamineo Phosphatidyl serineo Phosphatidyl inositolo Phosphatidic acido Cardiolipino Plasmalogeno Platelet activating factoro Phosphatidyl Glycerol2)Sphingophospholipids- Sphingol is the alcohol groupExample- Sphingomyelin Biochemistry for medics 6/29/2012 48
  49. 49. 1) Phosphatidylcholines (Lecithins )Phosphoacylglycerols containing choline are themost abundant phospholipids of the cellmembrane Are present a large proportion of the bodysstore of choline. Choline is important in nervoustransmission, as acetylcholine, and as a store oflabile methyl groupsDipalmitoyl lecithin is a very effective surface-active agent and a major constituent of thesurfactant preventing adherence, due to surfacetension, of the inner surfaces of the lungs. Itsabsence from the lungs of premature infantscauses respiratory distress syndrome. Biochemistry for medics 6/29/2012 49
  50. 50. Biochemistry for medics 6/29/2012 50
  51. 51. 2) Phosphatidyl ethanolamine (cephalin)- Structurally similar to Lecithin with the exceptionthat the base Ethanolamine replaces cholineBrain and nervous tissue are rich in Cephalin3) Phosphatidyl Serine-(found in most tissues) differfrom phosphatidylcholine only in that serine replacescholine4) Phosphatidylinositol -The inositol is present inphosphatidylinositol as the stereoisomer,myoinositol.Phosphatidylinositol 4,5-bisphosphate isan important constituent of cell membranephospholipids; upon stimulation by a suitablehormone agonist, it is cleaved into diacylglycerol andinositol trisphosphate, both of which act as internalsignals or second messengers. Biochemistry for medics 6/29/2012 51
  52. 52. Biochemistry for medics 6/29/2012 52
  53. 53. 5) Cardiolipin –Abundantly found in mitochondrial membrane.This is the only phospholipid with antigenicproperties.6) Plasmalogens –constitute as much as 10% of the phospholipidsof brain and muscle.Structurally, the plasmalogens resemblephosphatidylethanolamine but possess an etherlink on the sn-1 carbon instead of the ester linkfound in acylglycerols.Typically, the alkyl radical is an unsaturatedalcohol .In some instances, choline, serine, or inositol maybe substituted for ethanolamine. for medics 6/29/2012 Biochemistry 53
  54. 54. 7) Platelet activating factor (PAF)-Ether glycerophospholipidContains an unsaturated alkyl group in an ether link to carbon -1An acetyl residue at carbon 2 of the glycerol backbone.Synthesized and released by various cell typesPAF activates inflammatory cells and mediates hypersensitivity,acute inflammatory and anaphylactic reactionsCauses platelets to aggregate and degranulate and neutrophilsand alveolar macrophages to generate superoxide radicals8) Phosphatidyl Glycerol-Formed by esterification of phosphatidic acid with glycerolDiphosphatidyl glycerol, cardiolipin is found in the mitochondrialmembrane Biochemistry for medics 6/29/2012 54
  55. 55. Sphingomyelin-Backbone is sphingosine(amino alcohol)A long chain fatty acid isattached to amino group ofsphingosine to form CeramideThe alcohol group at carbon-1of sphingosine is esterified tophosphoryl choline, producingsphingomyelinSphingomyelin is animportant component ofmyelin of nerve fibers Biochemistry for medics 6/29/2012 55
  56. 56. Components of cell membrane, mitochondrial membrane andlipoproteinsParticipate in lipid absorption and transportation from intestinePlay important role in blood coagulation Required for enzyme action- especially in mitochondrialelectron transport chainCholine acts as a lipotropic agentMembrane phospholipids acts as source of Arachidonic acidAct as reservoir of second messenger- Phosphatidyl InositolAct as cofactor for the activity of Lipoprotein lipasePhospholipids of myelin sheath provide insulation around thenerve fobersDipalmitoyl lecithin acts as a surfactant Biochemistry for medics 6/29/2012 56
  57. 57. L/S Ratio in amniotic fluid is used for the evaluationof fetal lung maturityPrior to 34 weeks gestation, lecithin andsphingomyelin concentrations are equal butafterwards there is marked increase in Lecithinconcentration.A L/S ratio of> 2 or > 5 indicates adequate fetallung maturityDelivery of a premature,low birth weight baby withlow L/S ratio (1 or<1) predisposes the child torespiratory distress syndrome Biochemistry for medics 6/29/2012 57
  58. 58. Glycolipids differ from sphingomyelins in that theydo not contain phosphoric acid and the polar headfunction is provided by monosaccharide oroligosaccharide attached directly to ceramide by anO- glycosidic linkage.The number and type of carbohydrate moietiespresent, determine the type of glycosphingolipid.There are two types of Glycolipids-A) Neutral glycosphingolipidsB) Acidic glycosphingolipids Biochemistry for medics 6/29/2012 58
  59. 59. Cerebrosides- These are ceramidemonosaccharides, that contain either amolecule of galactose(Galactocerebroside)orglucose(Glucocerebroside)Found predominantly in the brain andnervous tissue with high concentration inmyelin sheathCeramide oligosaccharides (Globosides) areproduced by attaching additionalmonosaccharides to Glucocerebroside.Lactosyl ceramide contains lactose(Galactose and Glucose attached to ceramide) Biochemistry for medics 6/29/2012 59
  60. 60. Cerebrosides (Contd.) – Individualcerebrosides are differentiated on the basisof kind of fatty acids in the molecule. Fourtypes are commonly observed-a) Kerasin- contains Lignoceric acidb) Cerebron- Contains cerebronic acidc) Nervon- contains Nervonic acidd) Oxynervon- contains hydroxy derivative of nervonic acid Biochemistry for medics 6/29/2012 60
  61. 61. Biochemistry for medics 6/29/2012 61
  62. 62. They are negatively charged at physiological pHThe negative charge is imparted by N- acetylNeuraminic acid(Sialic acid)Brain gangliosides may contain up to four Sialic acidresidues and based on that they are-GM, GD, GT andGQ, containing 1,2,3 or 4 Sialic acid residuesFour important types of Gm series are-GM1, GM2 and GM3GM1 is complex of all Biochemistry for medics 6/29/2012 62
  63. 63. Biochemistry for medics 6/29/2012 63
  64. 64. They occur particularly in the outer leaflet of theplasma membrane, where they contribute to cellsurface carbohydrates.They act as cell surface receptors for varioushormones, and growth factorsPlay important role in cellular interactions, growthand developmentThey are source of blood group antigens andvarious embryonic antigensGM1 acts as a receptor for cholera toxin in humanintestine Biochemistry for medics 6/29/2012 64
  65. 65.  They are cerebrosides that contain sulfatedgalactosyl residuesNegatively charged at physiological pHFound predominantly in nerve tissue andkidneyFailure of degradation causes them toaccumulate in nervous tissues Biochemistry for medics 6/29/2012 65
  66. 66. Disease Enzyme deficiency Nature of lipid Clinical accumulated SymptomsTay Sach‘s Disease Hexosaminidase A GM2 Ganglioside Mental retardation, blindness, muscular weaknessFabrys disease α-Galactosidase Globotriaosylceramide Skin rash, kidney failure (full symptoms only in males; X-linked recessive).Metachromatic Arylsulfatase A Sulfogalactosylceramid Mental retardationleukodystrophy e and Psychologic disturbances in adults; demyelination. Biochemistry for medics 6/29/2012 66
  67. 67. Disease Enzyme Nature of lipid Clinical deficiency accumulated symptomsKrabbes disease β-Galactosidase Galactosylceramide Mental retardation; myelin almost absent.Gauchers disease β -Glycosidase Glucosyl ceramide Enlarged liver and spleen, erosion of long bones, mental retardation in infants.Niemann-Pick Sphingomyelinase Sphigomyelin Enlarged liver anddisease spleen, mental retardation; fatal in early life.Farbers disease Ceramidase Ceramide Hoarseness, dermatitis, skeletal deformation, mental retardation; fatal in early life Biochemistry for medics 6/29/2012 67
  68. 68.  Fatty acids, phospholipids, sphingolipids, bile salts, and, to a lesser extent, cholesterol contain polar groups. Therefore, part of the molecule is hydrophobic, or water-insoluble; and part is hydrophilic, or water-soluble. Such molecules are described as amphipathic They become oriented at oil:water interfaces with the polar group in the water phase and the nonpolar group in the oil phase. A bilayer of such amphipathic lipids is the basic structure in biologic membranes Biochemistry for medics 6/29/2012 68
  69. 69.  Liposomes-Liposomes may be formed by sonicating an amphipathic lipid in an aqueous medium. They consist of spheres of lipid bilayers that enclose part of the aqueous medium. Liposomes are of potential clinical use— particularly when combined with tissue-specific antibodies—as carriers of drugs in the circulation, targeted to specific organs, eg, in cancer therapy. In addition, they are used for gene transfer into vascular cells and as carriers for topical and transdermal delivery of drugs and cosmetics. Biochemistry for medics 6/29/2012 69
  70. 70.  Emulsions -are much larger particles, formed usually by nonpolar lipids in an aqueous medium. These are stabilized by emulsifying agents such as amphipathic lipids (eg, lecithin), which form a surface layer separating the main bulk of the nonpolar material from the aqueous phase . Biochemistry for medics 6/29/2012 70
  71. 71. Biochemistry for medics 6/29/2012 71