生物化学教学课件：Lipid 脂质

1、Lipid 脂质1. IntroductionBiological lipids are a chemically diverse group of compounds.The common and defining feature of which is their insolubility in water. The biological functions of the lipids are as diverse as their chemistry. You should know Representative lipids of each type chemical structur

2、e biological function physical propertiesClassification of biological lipids:By chemical composition:Simple lipidCompound lipidDerived lipidSimple lipid: FA+alcohol 甘油三酯 TG: Glycerol + FA 腊 Wax: long chain alcohol +FA Compound lipid alcohol + FA+ non lipid component Phospholipid磷脂-phosphate/head gro

3、up Glycolipids 糖脂-saccharide磷脂甘油磷脂鞘氨脂鞘氨醇糖脂半乳糖脂，脑苷脂鞘氨脂Derived lipidDerivatives of these compounds取代烃 fatty acids and their salts 脂肪酸(盐)固醇类 steroid hormones, sterol固醇, taurocholic acid胆酸Terpene萜 pigment，香精油，天然橡胶其他： lipid-soluble vitamins(Vit A,D,E,K), lipoprotein, prostaglandinsClassification of biolo

4、gical lipids:By biological function1.Storage lipids: fats and oils, wax2.Structural lipids in membranes: phospholipids, glycolipids and sterols3.Active lipid: Vitamin, hormone, cofactors, pigments and so on.2. Storage lipidStorage lipid are derivatives of fatty acids.Triacylglycerols: fatty acid est

5、ers of glycerol WaxFatty acid脂肪酸 Fatty acids in the body biosynthesis from acetyl-CoA breakdown of fats and phospholipidsFree fatty acids are rarely found in the bodyThey are transported in the blood complexed to serum albumin血清清蛋白Common fatty acids-Carbon atoms: 12-24, even Synthesis of fatty acids

6、, condensation of two-carbon unitsLocation of double bond: 9,12,15,A simplified nomenclature18:2 (9c,12c) C-cis T-trans18-carbon,C-1 being the carboxyl carbonOne double bond between C-9 and C-10Another between C-12 and C-13Linoleic acid 亚油酸Palmitic acid 棕榈酸，软脂酸 十六烷酸 16-carbon saturated fatty acid 16

7、:0Stearic acid 硬脂酸 十八烷酸 18-carbon saturated fatty acid 18:0Oleic acid 油酸，顺-9-十八碳烯酸18-carbon fatty acid, a single double bond18:19cPhysical properties of fatty acids saturated (no double bonds) unsaturated (contain one or more double bonds)Almost all biologically produced unsaturated fatty acids cont

8、ain cis double bonds-a bend in the molecules the length The hydrocarbon chain degree of unsaturation solubilityPhysical properties melting pointThe longer the fatty acyl chain, the fewer the double bonds, the lower is the solubilityThe longer the fatty acyl chain, the fewer the double bonds, the hig

9、her is the melting pointMelting pointAt room temperatureSaturated fatty acid-a waxy consistencyUnsaturated fatty acid-oily liquids Free rotation,Molecules can pack together tightly in nearly crystalline arraysKinkTakes less thermal energy to disorder markedly lower melting pointsStearic acid 18:0 70

10、 Palmitic acid 16:0 63 oleic acid油酸18:19c 13.4 Linoleic acid亚油酸18:29,12c -5 Linoleic acid亚麻酸18:39,12,15c -11 Trans-oleic acid 油酸18:19t 44 反式双键不引起键的弯折nearly all naturally occurring unsaturated fatty acids, the double bonds are in the cis configuration cis transDiets high in trans fatty acids correlat

11、e with increased blood levels of LDL(bad cholesterol), it is generally recommended that one avoid large amountsFrench fries, doughnuts and cookies tend to be high in trans fatty acidsmelting point of branched FAStearic acid 7010-methyl-stearic acid 10 Essential fatty acidsLinoleic acid 亚油酸 顺9，12-十八碳

12、二烯酸18:2 9c,12c-6 PUFA (poly-unsaturated fatty acid), relate to skin disease Linolenic acid 亚麻酸18:39c,12c,15c顺-9，12，15-十八碳三烯酸-3 PUFA deficiency -nerve and heart diseaseEPA 二十碳五烯酸DHA 二十二碳六烯酸AA 花生四烯酸can be synthesized by Linoleic acid or linolenic acid TG(triacylglycerols)Three fatty acids are esterifi

13、ed to glycerol fat (solid at room temperature) oil (liquid at room temperature)Store energy TG fatty acids + glycerollipases脂肪酶triacylglycerolsSimpleMixed NonpolarHydrophobic moleculesMany Foods Contain TriacylglycerolsLipid rancid: oxidative cleavage of the double bonds in unsaturated fatty acids p

14、roduces aldehydes and carboxylic acids of shorter chain.Triacylglycerols provide stored energy and insulationFour guinea pig 豚鼠 adipocytesCotyledon子叶cell from a seed of the Arabidopsis拟南芥TGlipaseFatty acid + glycerolmitochondrion-oxidationATPStored fuelsTriacylglycerols vs polysaccharidesa. More red

15、uced-yields more energyb. hydrophobic-unhydrated-not have to carry the extra weight of water of hydration stored polysaccharides(2g water per gram of polysaccharidese.g.Obese people of 15-20kg triacylglycerols meet energy needs for months 15-20kg glycogen-less than a days energy supplyc. Carbohydrat

16、esReady solubility in water-quick sources of metabolic energyInsulation against low temperatures warm-blooded polar animals are amply padded with triacylglycerols hibernating animals (bears ) insulation and energy storageTG-Sperm Whales: Fatheads of the DeepHead:1/3 body weight90% of the head is spe

17、rmaceti oil, 4 tonsTriacylglycerols + waxesBuoyancyWax: waxes serve as water repellentsEsters fatty acids: long-chain (C14-C36) saturated and unsaturated Alcohols: long-chain(C16 to C30)Melting points (60-100)工蜂腹部的蜡腺分泌 a honeycombConstructed of bees wax蜂蜡，is firm at 25 and completely impervious to w

18、ater3. Structural Lipids in MembranesGlycerophospholipidsGalactolipids and sulfolipids Archaebacterial tetraether lipidsSphingolipidsSterolsGlycerophospholipids甘油磷脂Glycerol 3-phosphate磷酸甘油+FA (R1, R2) 磷脂酸derivatives of phosphatidic acid 磷脂酸The backbone of glycerophospholipidsA highly polarCharged gr

19、oupA phosphodiester磷酸二酯 linkage to the third carbonIn general:At C-1-C16 or C18 saturated fatty acidAt C-2-C18 to C20 unsaturated fatty acid.Phosphatidic acid 磷脂酸，is the parent compound磷脂酸磷脂酰肌醇4，5-二磷酸磷脂酰磷脂酰甘油磷脂酰甘油心磷脂卵磷脂脑磷脂The common glycerophospholipids甘油磷脂Diacylglycerols二脂酰甘油Head-group alcoholsEach

20、 derivative is named for: the head-group (X) the prefix “phosphatidyl-”Phosphodiester bondGlycerophospholipids Differ in the structure of their head group The polar heads carry electric charges at pH near 7Some Phospholipids Have Ether-Linked Fatty AcidsOne of the two acyl chains is attached to glyc

21、erol in ether linkage.The ether-linked chain may be saturated, or may contain a double bond between C-1 and C-2. Half of the heart phospholipids are plasmalogens（缩醛磷脂）. platelet-activating factor, is a potent molecular signal. released from basophils嗜碱性粒细胞 stimulates platelet aggregation release of

22、serotonin (a vasoconstrictor血管收缩剂) from platelets. important in inflammation and the allergic response.Galactolipids and Sulfolipidspredominate in plant cellsGalactolipids: localized in the thylakoid internal membranes of chloroplastsIn plant membraneCarries fixed negative chargeSulfolipids:Archaeba

23、cterial tetraether lipidsArchaebacteria, live in extreme conditionsether bonds-stable to hydrolysis at low pH and high temperature than are the ester bondsTwo polar heads(30-32 carbons) branched hydrocarbonsGlycerol dialkyl glycerol tetraethers (GDGTs) SphingolipidsSphingolipids Are Derivatives of S

24、phingosineSphingolipids are composed of: Long-chain amino alcohol sphingosine Long-chain fatty acid Polar headCeramide 神经酰胺 is the structural parent of all sphingolipids鞘脂类 (X=H)X基团：joined by a phosphodiester linkagesphingomyelinglycosidic linkage-glycosphingolipids鞘糖脂 鞘脂类鞘糖脂鞘脂类红细胞糖苷脂脑苷脂鞘磷脂神经酰胺神经节苷脂

25、Sphingomyelin 鞘磷脂Polar head group-phosphocholine/phosphoethanolamin, no net chargePresent in the plasma membranes of animal cells and are especially prominent in myelin脑髓鞘Resemble phosphatidylcholines卵磷脂 in general properties and three-dimensinal structureSphingomyelins鞘磷脂 phospholipidGlycerophospho

26、lipidsLipid bilayersForming membranes surrounding cells:The polar portions face outwards, towards waterThe nonpolar moieties associate with each other inside the bilayer.Lipids(glycerophospholipids, sphingolipids, cholesterol) proteins (enzyme) SacchridesH2OMetal ionThe Composition and Architecture

27、of MembranesA Lipid Bilayer Is the Basic Structural Element of MembranesMost cells continually degrade and replace their membraneLipids(phospholipids and sphingolipids) are degraded in lysosomes -specific hydrolytic enzymeGlycosphingolipids as determinants of blood groups. The human blood groups (O,

28、 A, B) are determined in part by the oligosaccharide head groups (blue) of these glycosphingolipids.Sphingolipids at Cell Surfaces Are Sites of Biological RecognitionSterols固醇Structural lipids present in the membranes of most eukaryotic cells环戊烷多氢菲为基础Four Fused carbon ringsThree-six carbons多氢菲One-fi

29、ve carbons 环戊烷 steroid nucleous 甾核Methyl group角甲基cholesterolSteroid nucleus -relatively rigidCholesterol 胆固醇animal tissuesSitosterol 谷固醇, stigmasterol豆固醇-plantsErgosterol 麦角固醇-fungie.g. Cholesterol胆固醇Membrane constituentsWeakly amphiphilic (few polar groups)A prominent component of lipid bilayers-Ch

30、olesterol inserted between fatty acyl side chainsreduces the fluidity of the bilayerincreases the thickness of the lipid leaflet.4. Lipid as signals, cofactors and pigments(1) Phosphatidylinositol bisphosphate 磷脂酰肌醇4，5-二磷酸 is hydrolyzed to yield two intracellular messengers:Diacylglycerol 二酰基甘油Inosi

31、tol肌醇-1，4，5-triphosphatePIP2磷脂酰肌醇4，5-二磷酸IP3 肌醇1,4,5-三磷酸DAG二酰基甘油(2) Eicosanoids类二十碳烷 Carry Messages to Nearby CellsProstaglandins前列腺素，thromboxane凝血噁烷, Leukotriene白三烯 are potent hormonesEicosanoids are paracrine旁分泌 hormones.Involved in reproductive function, inflammation, fever, pain; formation of blo

32、od clots regulation of blood pressure; gastric acid secretion; etc.Eicosanoids 类二十碳烷20碳的PUFA衍生而来凝血噁烷白三烯类化合物Local hormone, half life: sec- min花生四烯酸前列腺素PG (Prostaglandins)前列腺素Producing feverInflammationStimulate contraction of uterus-PGF2 引产PG, regulating the synthesis of the intracellular messenger c

33、AMP,cAMP mediates the action of diverse hormonesthe PG affect a wide range of cellular and tissue functions. Thromboxane凝血噁烷Produced by platelets act in the formation of blood clots and the reduction of blood flow to the site of a clot.Shut down the synthesis of PG消炎，镇痛，退热Inhibit the synthesis of th

34、romboxaneAnti blood-clottingnonsteroidal antiinflammatory drugs (NSAIDs)aspirin, ibuprofen, and meclofenamateprostaglandin H2 synthase (cyclooxygenase or COX)LeukotrienesPowerful biological signals. leukotriene induces contraction of the muscle lining the airways to the lung. Overproduction of leuko

35、trienes causes asthmatic attacks.Leukotriene synthesis is one target of antiasthmatic drugs such as prednisone强的松. (3) Steroid类固醇 hormones, derived from sterols固醇 serve as powerful bioloigical signals, such as the sex hormones.Prednisone泼尼松、强的松 and prednisolone can inhibit phospholipase A2inhibit ar

36、achidonate acid releaseinhibit the synthesis of Eicosanoids Drug of asthma and rheumatoid arthritis(4) Vitamins D,A,E and K are fat-soluble compounds made up of isoprene异戊二烯 units.Existed with the lipid in foods.Absorbed in the intestines with the lipidStored in the body, especially in the liverTerp

37、ene萜两个或多个异戊二烯(isoprene)连接而成C原子数10, 一般为5的倍数 单萜 10 倍半萜 15 二萜 20 三萜 30 四萜 40 -胡萝卜素 多聚萜 橡胶Vitamin Aderived from -carotene 胡萝卜素The alcohol form of vitamin A, retinol视黄醇, is the storage form in the body The aldehyde form, retinal视黄醛, has a role in vision.The acid form, retinoic acid视黄酸, functions in embry

38、onic development, epithelial cell development.Cells on retina: cone cells圆锥细胞: sensitive to bright light and colour rod cells杆细胞: sensitive to weak light, 暗视觉Lack of Vit A: night blindness夜盲症rhodopsinopsin11-cis-retinalAll trans-retinalisomeraseVitamin D抗佝偻病维生素derived from cholesterolD3 (most abunda

39、nt form), cholcalciferol胆钙化醇 Vitamin D is not technically a vitamin （not required in the diet. It arises from UV-photolysis of 7-dehydrocholesterol 7-脱氢胆固醇） Vitamin D regulates calcium and phosphorus metabolism, 有利于新骨的生成与钙化。Dietary vitamin D prevents ricketsVitamin D2 (ergocalciferol麦角钙化醇) is a comm

40、ercial product formed by UV irradiation of the ergosterol of yeast. Vitamin D2 is structurally similar to D3Vitamin E also called -tocopherol 生育酚,与动物生育有关an antioxidant protect against oxidative damage in cellular membranes. preventing the attack of peroxides 过氧化物, 过氧化氢on unsatured fatty acids in mem

41、brane lipidsTocopherols are found in eggs and vegetable oils and are especially abundant in wheat germ. Depleted of vitamin E develop scaly skin, muscular weakness and sterility.Vitamin EVitamin K 凝血维生素Vitamin K deficiency slows blood clotting, which can be fatal. Vitamin K deficiency is very uncomm

42、on in humans(5) Ubiquinones（泛醌，辅酶Q）and plastoquinones质体醌, electron carriers in mitochondria and chloroplasts叶绿体, respectively.5. Lipoprotein 脂蛋白 Lipid noncovalent bond 非共价键 Protein plasma lipoprotein 血浆脂蛋白 cellular lipoprotein 细胞脂蛋白血浆脂蛋白 plasma lipoproteinThe transport of lipids in blood:FAcombined with serum albumin Phospholipids, TG, cholesterols, etclipoprotein micronsLipoprotein structureCore: TG三酰