醫(yī)學(xué)細(xì)胞生物學(xué)：第二篇 細(xì)胞的結(jié)構(gòu)與功能

Location, structureMolecular componentsFunction AB細(xì)胞的生命活動(dòng)及生命現(xiàn)象：細(xì)胞的生命活動(dòng)及生命現(xiàn)象：簡(jiǎn)單說(shuō)包括生、老、病、死簡(jiǎn)單說(shuō)包括生、老、病、死具體說(shuō)包括細(xì)胞的分化、生長(zhǎng)與分裂、細(xì)胞的運(yùn)動(dòng)、遺傳與變異、細(xì)胞的具體說(shuō)包括細(xì)胞的分化、生長(zhǎng)與分裂、細(xì)胞的運(yùn)動(dòng)、遺傳與變異、細(xì)胞的物質(zhì)與能量代謝、細(xì)胞對(duì)外界刺激的應(yīng)答、細(xì)胞的衰老與死亡。物質(zhì)與能量代謝、細(xì)胞對(duì)外界刺激的應(yīng)答、細(xì)胞的衰老與死亡。細(xì)胞的結(jié)構(gòu)與功能細(xì)胞的結(jié)構(gòu)與功能第二篇第二篇 細(xì)胞的結(jié)構(gòu)與功能細(xì)胞的結(jié)構(gòu)與功能 細(xì)胞膜與物質(zhì)的跨膜運(yùn)輸細(xì)胞膜與物質(zhì)的跨膜運(yùn)輸 細(xì)胞內(nèi)膜系統(tǒng)與囊泡轉(zhuǎn)運(yùn)細(xì)胞內(nèi)膜系統(tǒng)與囊泡轉(zhuǎn)運(yùn) 線粒體與細(xì)胞能量轉(zhuǎn)換線粒體與細(xì)胞能量轉(zhuǎn)換 細(xì)胞核細(xì)胞核 細(xì)胞骨架與細(xì)胞的運(yùn)動(dòng)細(xì)胞骨架與細(xì)胞的運(yùn)動(dòng) 細(xì)胞與細(xì)胞粘連細(xì)胞與細(xì)胞粘連 細(xì)胞外基質(zhì)及功能細(xì)胞外基質(zhì)及功能 第四章第四章 細(xì)胞膜與物質(zhì)的跨膜運(yùn)輸細(xì)胞膜與物質(zhì)的跨膜運(yùn)輸細(xì)胞膜的化學(xué)組成與分子特點(diǎn)；細(xì)胞膜的化學(xué)組成與分子特點(diǎn)；小分子物質(zhì)的跨膜運(yùn)輸小分子物質(zhì)的跨膜運(yùn)輸;大分子與顆粒物質(zhì)的跨膜運(yùn)輸；大分子與顆粒物質(zhì)的跨膜運(yùn)輸；細(xì)胞表面及特化結(jié)構(gòu)；細(xì)胞表面及特化結(jié)構(gòu)；細(xì)胞膜異常與疾病細(xì)胞膜異常與疾病 細(xì)胞膜細(xì)胞膜第一節(jié)第一節(jié) 細(xì)胞膜的化學(xué)組成與分子結(jié)構(gòu)細(xì)胞膜的化學(xué)組成與分子結(jié)構(gòu)一一. 細(xì)胞膜的化學(xué)組成細(xì)胞膜的化學(xué)組成（一）膜脂構(gòu)成細(xì)胞膜的基本骨架（一）膜脂構(gòu)成細(xì)胞膜的基本骨架膜脂（膜脂（membrane lipid）磷脂磷脂膽固醇膽固醇糖脂糖脂第一節(jié)第一節(jié) 細(xì)胞膜的化學(xué)組成與分子結(jié)構(gòu)細(xì)胞膜的化學(xué)組成與分子結(jié)構(gòu)一一. 細(xì)胞膜的化學(xué)組成細(xì)胞膜的化學(xué)組成（一）膜脂構(gòu)成細(xì)胞膜的基本骨架（一）膜脂構(gòu)成細(xì)胞膜的基本骨架膜脂（膜脂（membrane lipid）磷脂磷脂膽固醇膽固醇糖脂糖脂F(xiàn)igure 10-3 Molecular Biology of the Cell ( Garland Science 2008)PE PSPCFigure 10-3 Molecular Biology of the Cell ( Garland Science 2008)PE PSPCFigure 10-3 Molecular Biology of the Cell ( Garland Science 2008)PE PSPCFigure 10-3 Molecular Biology of the Cell ( Garland Science 2008)PE PSPCFigure 10-18 Molecular Biology of the Cell ( Garland Science 2008)Figure 10-4 Molecular Biology of the Cell ( Garland Science 2008)膜脂膜脂磷脂：膜脂的基本成分，磷脂：膜脂的基本成分，50%膽固醇：穩(wěn)定膜和調(diào)節(jié)膜的流動(dòng)性膽固醇：穩(wěn)定膜和調(diào)節(jié)膜的流動(dòng)性糖脂：糖脂：5% 以下，位于細(xì)胞的膜外以下，位于細(xì)胞的膜外Figure 10-5 Molecular Biology of the Cell ( Garland Science 2008)Figure 10-3. A lipid micelle and a lipid bilayer seen in cross-section. Lipid molecules form such structures spontaneously in water. The shape of the lipid molecule determines which of these structures is formed. Wedge-shaped lipid molecules (above) form micelles, whereas cylinder-shaped phospholipid molecules (below) form bilayers.Figure 10-11 Molecular Biology of the Cell ( Garland Science 2008)Figure 10-12 Molecular Biology of the Cell ( Garland Science 2008)The importance of the lipid bilayer The lipids of a membrane are more than simple structural elements: It is a skeleton of the membrane Lipid composition can determine the physical state of the membrane and influence the activity of particular membrane proteins. Membrane lipids also provide the precursors for highly active chemical messengers that regulate cellular function.Figure 10-1c Molecular Biology of the Cell ( Garland Science 2008)（二）膜蛋白執(zhí)行細(xì)胞膜的多種重要的功能（二）膜蛋白執(zhí)行細(xì)胞膜的多種重要的功能膜蛋白膜蛋白內(nèi)在膜蛋白（內(nèi)在膜蛋白（intrinsic membrane protein）整合膜蛋白（整合膜蛋白（integral membrane protein）外在膜蛋白外在膜蛋白(extrinsic membrane protein)脂錨定蛋白（脂錨定蛋白（lipid anchored protein)外周蛋白（外周蛋白（peripheral protein）脂連接蛋白（脂連接蛋白（lipid-linked protein）（三）膜糖類覆蓋了細(xì)胞膜表明（三）膜糖類覆蓋了細(xì)胞膜表明二二. 細(xì)胞膜的特性細(xì)胞膜的特性1. 膜脂的不對(duì)稱性膜脂的不對(duì)稱性2. 膜蛋白的不對(duì)稱性膜蛋白的不對(duì)稱性3. 膜糖的不對(duì)稱性膜糖的不對(duì)稱性（一）不對(duì)稱性（一）不對(duì)稱性（二）膜的流動(dòng)性是膜功能活動(dòng)的保證（二）膜的流動(dòng)性是膜功能活動(dòng)的保證fluidity1. 膜脂雙分子層是二維流體膜脂雙分子層是二維流體液晶態(tài)（液晶態(tài)（liquid-crystal state)2. 膜脂分子能進(jìn)行多種運(yùn)動(dòng)膜脂分子能進(jìn)行多種運(yùn)動(dòng)3. 多種因素影響膜脂的流動(dòng)性多種因素影響膜脂的流動(dòng)性（1）脂肪酸鏈的飽和程度）脂肪酸鏈的飽和程度（2）脂肪酸鏈的長(zhǎng)短）脂肪酸鏈的長(zhǎng)短（3）膽固醇的雙重調(diào)節(jié)作用）膽固醇的雙重調(diào)節(jié)作用（4）卵磷脂與鞘磷脂的比例）卵磷脂與鞘磷脂的比例（5）膜蛋白的影響）膜蛋白的影響相變溫度相變溫度上上，減慢運(yùn)動(dòng)，減慢運(yùn)動(dòng)相變溫度相變溫度下下，促進(jìn)運(yùn)動(dòng)，促進(jìn)運(yùn)動(dòng)相變溫度的概念相變溫度的概念4. 膜蛋白的運(yùn)動(dòng)性膜蛋白的運(yùn)動(dòng)性（1）側(cè)向運(yùn)動(dòng)）側(cè)向運(yùn)動(dòng)（2）旋轉(zhuǎn)運(yùn)動(dòng)）旋轉(zhuǎn)運(yùn)動(dòng)三三. 細(xì)胞膜的分子結(jié)構(gòu)模型細(xì)胞膜的分子結(jié)構(gòu)模型最初發(fā)現(xiàn)膜雙層磷脂結(jié)構(gòu)的是最初發(fā)現(xiàn)膜雙層磷脂結(jié)構(gòu)的是E. Gorter 和和Grendel 從血影中從血影中提取脂質(zhì)提取脂質(zhì)。（一）片層結(jié)構(gòu)模型（一）片層結(jié)構(gòu)模型To account for permeability of membrane to non-lipid substances, Danielli and Davson proposed sandwich model (later proved wrong) with phospholipid bilayer between layers of protein. （二）單位膜模型（二）單位膜模型20世紀(jì)世紀(jì)50s J.D Robertson（三）（三）流動(dòng)鑲嵌模型流動(dòng)鑲嵌模型 fluid-mosaic model In 1972, Singer and Nicolson introduced the currently accepted fluid-mosaic model of membrane structure. In this model, a flexible layer made of lipid molecules is interspersed with large protein molecules that act as channels, transporters through which other molecules enter and leave the cell. There are also receptors in the membrane. The core lipid bilayer exists in a fluid state, capable of dynamic movement. Membrane proteins form a mosaic of particles penetrating the lipid to varying degree模型強(qiáng)調(diào)了膜的流動(dòng)性及不對(duì)稱性模型強(qiáng)調(diào)了膜的流動(dòng)性及不對(duì)稱性1975年年 D.F Wallach 提出了一種提出了一種“晶格鑲嵌模型晶格鑲嵌模型” （crystal mosaic model)1977年年M.KJain 和和H.B White 又提出了又提出了“板塊鑲嵌模型板塊鑲嵌模型”（block mosaic model）（四）脂筏模型（嚴(yán)格說(shuō)，它不是模型而是一種特殊的結(jié)構(gòu)）四）脂筏模型（嚴(yán)格說(shuō)，它不是模型而是一種特殊的結(jié)構(gòu)）第二節(jié)第二節(jié) 小分子物質(zhì)的跨膜運(yùn)輸小分子物質(zhì)的跨膜運(yùn)輸一一. 膜的選擇性通透和簡(jiǎn)單擴(kuò)散膜的選擇性通透和簡(jiǎn)單擴(kuò)散二二.膜轉(zhuǎn)運(yùn)蛋白介導(dǎo)的跨膜運(yùn)輸膜轉(zhuǎn)運(yùn)蛋白介導(dǎo)的跨膜運(yùn)輸膜轉(zhuǎn)運(yùn)蛋白（膜轉(zhuǎn)運(yùn)蛋白（membrane transport protein）Carrier ProteinChannel Protein（一）離子通道轉(zhuǎn)移各種離子（一）離子通道轉(zhuǎn)移各種離子Ion channel Passive transport Specificity for the ion size and chargeHigh speed of transporting , 106 to 108 /secondConformation changes from opening to closingK+漏通道漏通道, 是持續(xù)開放的，大多數(shù)離子通道是受是持續(xù)開放的，大多數(shù)離子通道是受閘門閘門控制的控制的Figure 11-31 Molecular Biology of the Cell ( Garland Science 2008)（二）載體蛋白介導(dǎo)的易化擴(kuò)散（二）載體蛋白介導(dǎo)的易化擴(kuò)散Facilitated diffusion（三）（三）載體蛋白介導(dǎo)的主動(dòng)運(yùn)輸載體蛋白介導(dǎo)的主動(dòng)運(yùn)輸1.離子泵直接水解離子泵直接水解ATP進(jìn)行主動(dòng)運(yùn)輸進(jìn)行主動(dòng)運(yùn)輸鈣泵鈣泵2. 離子驅(qū)動(dòng)的協(xié)同運(yùn)輸離子驅(qū)動(dòng)的協(xié)同運(yùn)輸Cotransport: coupled transport A special kind of active transport Two molecules travel together, one as a passenger, the other as a driver. The driver diffuses down its electrochemical gradient, but it cannot do so unless it has the passenger. ATP is not directly involved, but it sets up the electrochemical gradient used to propel the driver.Symport The passenger and the driver are transported in the same direction. Na-glucose symport takes place in the intestine, from the gut lumen to the insides of the cells lining the gut.Antiport The driver and passenger travel in opposite directions.Na+-H+ exchange carrierCl-HCO3- exchangerThe energy of ATP may be used directly or indirectly.Direct Active Transport. Some transporters bind ATP directly and use the energy of its hydrolysis to drive active transport. Indirect Active Transport. Other transporters use the energy already stored in the gradient of a directly-pumped ion. Direct active transport of the ion establishes a concentration gradient. When this is relieved by facilitated diffusion, the energy released can be harnessed to the pumping of some other ion or molecule.第三節(jié)第三節(jié) 大分子和顆粒物質(zhì)大分子和顆粒物質(zhì)的跨膜運(yùn)輸?shù)目缒み\(yùn)輸EndocytosisExocytosis一一. 胞吞作用胞吞作用（一）（一） 吞噬作用吞噬作用phagocytosisA. Phagocytosis Cell eating: cells engulf particles with pseudopodia and pinches off a food vacuole. Two examples:1. White Blood Cell2. AmoebaWhite Blood CellBacteria Phagocytosis: The uptake of large particles vIncluding: macromolecules, cell debris, even microorganisms and other cells.vPhagocytosis is usually restricted to specialized cells called Phagocytes.vPhagocytosis is initiated by cellular contact with an appropriate target.vPhagocytosis may be stimulated by the opsoninsvPhagocytosis is driven by contractile activities of MF.（二）胞飲作用（二）胞飲作用PinocytosisB. Pinocytosis Cell drinking: droplets of extracellular fluid are absorbed into the cell by small vesicles. Example:Food Particles（三）受體介導(dǎo)的內(nèi)吞作用（三）受體介導(dǎo)的內(nèi)吞作用C. Receptor-Mediated Endocytosis Importing specific macromolecules (hormones) into the cell by the inward budding of vesicles formed from coated pits (receptors). HormonesReceptorsLiver Cell In most animal cells, clathrin-coated pits and vesicles provide an efficient pathway for taking up specific macromolecules from the extracellular fluid. In this process the macromolecules bind to complementary transmembrane receptor proteins, accumulate in coated pits, and then enter the cell as receptor-macromolecule complexes in clathrin-coated vesicles. Receptor-mediated endocytosis provides a selective concentrating mechanism that increases the efficiency of internalization of particular ligands more than a hundredfold, so that even minor components of the extracellular fluid can be specifically taken up in large amounts without taking in a correspondingly large volume of extracellular fluid. clathrin二二. 胞吐作用胞吐作用（一）結(jié)構(gòu)性分泌途徑（一）結(jié)構(gòu)性分泌途徑（constitutive secretion pathway)（二）（二）條件性分泌途徑（條件性分泌途徑（regulated secretion pathway)第四節(jié)第四節(jié) 細(xì)胞表面及其特化結(jié)構(gòu)細(xì)胞表面及其特化結(jié)構(gòu)一一. 細(xì)胞外被和胞質(zhì)溶膠細(xì)胞外被和胞質(zhì)溶膠Cell coat or glycocalyx 二二.細(xì)胞表面的特化結(jié)構(gòu)細(xì)胞表面的特化結(jié)構(gòu)1.微絨毛微絨毛2. 纖毛與鞭毛纖毛與鞭毛3. 褶皺（褶皺（ruffe)或片狀偽足（或片狀偽足（lamellipodium)第五節(jié)第五節(jié) 細(xì)胞膜異常與疾病細(xì)胞膜異常與疾病一一. 載體蛋白異常與疾病載體蛋白異常與疾病1. 胱氨酸尿癥（胱氨酸尿癥（cystinuria)膜轉(zhuǎn)運(yùn)體異常疾病，遺傳性膜轉(zhuǎn)運(yùn)體異常疾病，遺傳性病人腎小管上皮轉(zhuǎn)運(yùn)病人腎小管上皮轉(zhuǎn)運(yùn)胱氨酸胱氨酸及二氨基氨基酸（及二氨基氨基酸（賴氨酸，精氨酸賴氨酸，精氨酸及鳥氨酸及鳥氨酸）的載體蛋白缺陷而）的載體蛋白缺陷而 引起的疾病。引起的疾病。pH5-7 時(shí)，胱氨酸的飽和濃度為時(shí)，胱氨酸的飽和濃度為0.3-0.4g/L 2. 腎性糖尿腎性糖尿（renal glycosuria)二二. 離子通道異常與疾病離子通道異常與疾病Cystic fibrosis， CF三三.膜受體異常與疾病膜受體異常與疾病1. 家族性高膽固醇血癥家族性高膽固醇血癥（familial hypercholesterolemina)2. 重癥肌無(wú)力（重癥肌無(wú)力（myasthenia gravis)自身免疫疾病，自身免疫疾病， 體內(nèi)產(chǎn)生了抗體內(nèi)產(chǎn)生了抗N-Ach 受體的抗體。受體的抗體。2. 重癥肌無(wú)力（重癥肌無(wú)力（myasthenia gravis)自身免疫疾病，自身免疫疾病， 體內(nèi)產(chǎn)生了抗體內(nèi)產(chǎn)生了抗N-Ach 受體的抗體。受體的抗體。3. 癌變和細(xì)胞表面的關(guān)系癌變和細(xì)胞表面的關(guān)系（1） 接觸抑制喪失接觸抑制喪失（2）細(xì)胞的組成異常）細(xì)胞的組成異常膜脂的改變：膜脂的改變：Gm3 Gd3膜蛋白的改變膜蛋白的改變（3）抗原性的改變）抗原性的改變（4）與外源性凝集素的反應(yīng)）與外源性凝集素的反應(yīng)小結(jié)：小結(jié)：組成組成模型模型小分子物質(zhì)的運(yùn)輸小分子物質(zhì)的運(yùn)輸大分子物質(zhì)的運(yùn)輸大分子物質(zhì)的運(yùn)輸被動(dòng)運(yùn)輸被動(dòng)運(yùn)輸主動(dòng)運(yùn)輸（載體介導(dǎo)運(yùn)輸主動(dòng)運(yùn)輸（載體介導(dǎo)運(yùn)輸）自由擴(kuò)散自由擴(kuò)散離子通道離子通道載體介導(dǎo)的易化擴(kuò)散載體介導(dǎo)的易化擴(kuò)散離子泵離子泵協(xié)同運(yùn)輸協(xié)同運(yùn)輸symport antiportexcytosisendocytosisphagocytosispinocytosisReceptor mediated endocytosis細(xì)胞表面：細(xì)胞表面： 細(xì)胞外被（細(xì)胞外被（cell coat）或糖萼（）或糖萼（ glycocalyx）細(xì)胞表面的特化結(jié)構(gòu)細(xì)胞表面的特化結(jié)構(gòu)microvillusCillia or flagellaRuffle or lamellipodium細(xì)胞膜與疾病細(xì)胞膜與疾病