《细胞器与疾病》ppt课件

1、细胞器与疾病分子医学A mammalian cell The nucleus is a membrane bound structure that contains the cells hereditary information and controls the cells growth and reproduction. It is commonly the most prominent organelle in the cellThe nuclear content is located in the nuclear lumen and is surrounded by a double

2、 membrane or nuclear envelope, composed of inner membrane and outer membrane.The outer membrane is contiguous with the ERThe nuclear membrane contains nuclear pores, which provide selective access into and out of the nuclear lumenThe inner membrane has a protein lining called the nuclear lamina, whi

3、ch binds to chromatin and other nuclear components. The Nuclear Pore Complexes form a continuous aqueous channel between cytoplasm & nucleoplasm - nuclear pore complex is large about 120 million Daltons-30 different proteins found in pore; basic subunit repeated 16 times. “Central granule now ca

4、lled transporter functions to move molecules through pore. There is a ring of proteins that anchors pore to N.E. and the basket of fibers with unknown function no obvious motor proteins were found The region of the nucleus where portions of chromosomes that contain genes coding for ribosomal RNA are

5、 transcribed and ribosomal subunits are assembledbiology.about/library/weekly/aa032300a.htmStretch of DNA with rRNA genes nucleolar organizing region = (NOR) Ribosomal proteins are synthesized in cytoplasm and transported into the nucleusThese proteins self associate with appropriate rRNA during rRN

6、A synthesis forming immature ribosomal subunitsRibosomes finish self assembly in cytoplasm Endoplasmic ReticulumKEDLR-GFP激光共聚焦显微镜下的ERThe Endoplasmin Reticulum (ER) is an extensive, extra-nuclear membrane system with the following functions:ER is a home for various enzymes involved in protein folding

7、 , drug detoxification, membrane lipid biosynthesis, cholesterol and fatty acid metabolismER is an entry point for protein sorting. Targeting of these proteins is mediated by signal sequence. The membrane proteins are inserted into the ER membrane in their proper orientation. Secreted proteins are t

8、ranslocated into ER lumen and then transported to the destination place Rough and Smooth ERTwo regions of the ER differ in both structure and function. Rough ER has ribosomes attached to the cytoplasmic side of the membrane. Smooth ER lacks attached ribosomes. Typically, the smooth ER is a tubule ne

9、twork and the rough ER is a series of flattened :8001/esgbio/cb/org/er.gifThe smooth ER has a wide range of functions including carbohydrate and lipid synthesis. It serves as a transitional area for vesicles that transport ER products to various destinations. In liver cells the smoot

10、h ER produces enzymes that help to detoxify certain compounds. In muscles the smooth ER assists in the contraction of muscle cells and in brain cells it synthesizes male and female hormones. The rough ER manufactures membranes and secretory proteins The rough and smooth ER areUsually interconnected

11、and the proteinsand membranes made by the rough ER move into the smooth ER to be transferred to other locations. The cytoplasm has a reducing environment, while ER lumen is oxidizing . This difference is generated by unequal distribution of trypeptide glutathione and is essential for formation of di

12、sulfide bonds in proteins and for proper foldingER function-related diseases内质网应激与心血管疾病内质网与细胞凋亡内质网与PrP and Mad CowMitochondria (singular: mitochondrion) are the sites of aerobic respiration, and generally are the major energy production center in eukaryotesThe number of mitochondria range from one t

13、o thousands per cells.They are often positioned in cells nearest to sites of energy utilizationOne of the richest sources of mitochondria is a hummingbird flight muscleMitochondria are a double membrane organelle in which the inner membrane is in-folded to form “cristae. The outer membrane is a fair

14、ly simple phospholipid bilayer, containing porins, proteins that render it permeable to molecules of about 10 kilodaltons or less. Ions, nutrient molecules, ATP, ADP, etc. easily pass through the outer membrane and enter the intermembrane space The inner membrane is more complex and contains respira

15、tory chains and transportersThe matrix lies within the inner membrane. The access to this compartment often requires specific transportersFour possible localization for mitochondrial enzymesLocated near cell nucleus, consists of flattened, membrane-bounded sacs (cisternae) forming a stackEach stack

16、has:cis-face is an entry face - adjacent to ER to accept incoming vesiclestrans-face is an exit face points towards plasma membrane, produces vesicles for forward flowThe function of the Golgi is to transport and process secreted and membrane proteins from ER to the cell surfaceCis removal of mannos

17、e,phosphorylationMedial removal of mannose, addition of N-acetylglucosamineTrans Removal of galactose, addition of sialic acidTGN addition of sialic acid, SortingCisternae segregated into convex (cis), medial (middle), and concave (trans) compartments.ERcysmedialtransTGNGolgi structure/function/-rel

18、ated diseasesGolgi and MitosisGolgi and ApoptosisGolgi and Liver CancerHNE induces Golgi FragmentsControl30 min1 h2 h4 hLysosomes1、初级溶酶体、初级溶酶体 直径约直径约0.20.5um膜厚膜厚7.5nm，内含物均一，无，内含物均一，无明显颗粒，是高尔基体明显颗粒，是高尔基体分泌构成的如右图。分泌构成的如右图。含有多种水解酶，但没含有多种水解酶，但没有活性，只需当溶酶体有活性，只需当溶酶体破裂，或其它物质进入，破裂，或其它物质进入，才有酶活性。其水解酶才有酶活性。其水

19、解酶包括蛋白酶，核酸酶、包括蛋白酶，核酸酶、脂酶、磷酸酶、硫酸酯脂酶、磷酸酶、硫酸酯酶、磷脂酶类，知酶、磷脂酶类，知60余余种，这些酶均属于酸性种，这些酶均属于酸性水解酶，反响的最适水解酶，反响的最适PH值为值为5左右，溶酶体膜虽左右，溶酶体膜虽然与质膜厚度相近，但然与质膜厚度相近，但成分不同，成分不同，2、次级溶酶体、次级溶酶体 这些都是消化泡，正这些都是消化泡，正在进展或完成消化作在进展或完成消化作用的溶酶体，内含水用的溶酶体，内含水解酶和相应的底物，解酶和相应的底物，可分为自噬溶酶体可分为自噬溶酶体autophagolysosome和异噬溶酶体和异噬溶酶体phagolysosome，前者

20、消化的物质来自前者消化的物质来自细胞本身的各种组分细胞本身的各种组分,后者消化的物质来自后者消化的物质来自外源。外源。3、残体、残体 又称后溶酶体又称后溶酶体post-lysosome已失去酶已失去酶活性，仅留未消化的活性，仅留未消化的残渣故名，残体可经残渣故名，残体可经过外排作用排出细胞，过外排作用排出细胞，也能够留在细胞内逐也能够留在细胞内逐年增多，如肝细胞中年增多，如肝细胞中的脂褐质如右图。的脂褐质如右图。defects are called storage diseases. People with these disorders are missing one or more of

21、the lysosomal hydrolytic enzymes. 动物细胞溶酶体系统表示图 Lysosome-related diseases 溶酶体酶缺失或溶酶体酶的代谢环节缺点，影响细胞代谢，引起疾病。如台-萨氏Tay-Sachs等各种储积症隐性的遗传病。某些病原体麻疯杆菌、利什曼原虫或病毒被细胞摄入，进入吞噬泡但并未被杀死而繁衍抑制吞噬泡的酸化或利用胞内体中的酸性环境。类风湿性关节炎 溶酶体膜很易脆裂，其释放的酶导致关节组织损伤和发炎 。 矽肺 二氧化硅尘粒矽尘吸入肺泡后被巨噬细内吞噬，含有矽尘的吞噬小体与溶酶体合并成为次级溶酶体。二氧化硅的羟基与溶酶体膜的磷脂或蛋白构成氢键，导致吞噬

22、细胞溶酶体崩解，细胞本身也被破坏，矽尘释出，后又被其他巨噬细内吞噬，如此反复进展。受损或已破坏的巨噬细胞释放“致纤维化因子，并激活成纤维细胞，导致胶原纤维堆积，肺组织纤维化。Cytoskeleton is a network of protein filaments in the cytoplasmMain functions:Supports large volume of the cytoplasm. Participates in large-scale movements associated with the changes in cell shape and cell motili

23、ty.Provides machinery for organelle transport, chromasome segregation during mitosis, and cell division.Actin filamentsMicrotubulesIntermediate filaments Common Features : Linear polymers of protein subunits Actin ( 8 nm in diameter) Intermediate Filaments ( 10 nm in diameter) Microtubules ( 24 nm i

24、n diameter) Filaments are dynamic, i.e. they can assemble and disassemble Highly conserved Intermediate Filaments Intermediate filaments enable cells to withstand mechanical stress when cells are stretched. They can span the entire cytoplasm and are anchored to the plasma membrane.Also penetrates th

25、e entire volume of the cellWhereas actin fibers are concentrated at the periphery, most microtubules radiate from a central location in the cellMain functions: intracellular transport and mitosis Microtubules provide an organizational structure in an interphase cell and separate chromosomes in a div

26、iding /external/Frank.Gibbons/spindle.htmlMicrotubules Provide Tracks for TransportProtofilaments are linear chains of tubulin dimers, a parallel bundle of 13 protofilaments forms a microtubuleThere are three kinds of tubulins, each with many subtypes:a-tubulin and b-tubulin form a/

27、b tubulin dimers and represent the basic building block of microtubulesg-tubulin is involved in more specialized processes, such as nucleationMicrotubules have a GTP “cap stabilizing the ends.Motor Proteins Motor proteins bind to microtubules and move by cycles of conformational changes using energy

28、 from ATP. One end of the protein can bind to specific cellular components.Actin is the most common protein in the cytoplasmActin filaments are concentrated beneath the plasma membrane and give the cell mechanical strengthAssembly of actin filaments can determine cell shape and cause cell movementAs

29、sociation of actin filaments with myosin can form contractile structures核蛋白体核蛋白体 在粗面内质网外在粗面内质网外表的称固着核蛋白体，表的称固着核蛋白体，在细胞质内分散存在在细胞质内分散存在的称游离核蛋白体。的称游离核蛋白体。数个或致十个核蛋白数个或致十个核蛋白体聚集在一同称多聚体聚集在一同称多聚核蛋白体，系由信息核蛋白体，系由信息核糖核酸核糖核酸(mRNA)(mRNA)将核将核蛋白体串连在一同构蛋白体串连在一同构成。成。 核蛋白体在一定浓度的镁离子溶液内，可分核蛋白体在一定浓度的镁离子溶液内，可分成一大一小两个亚单位

30、。分别称为大亚基与小亚成一大一小两个亚单位。分别称为大亚基与小亚基，可用超速离心法将两者分开。两个亚基合在基，可用超速离心法将两者分开。两个亚基合在一同时，由于一大一小，构成葫芦状。核蛋白体一同时，由于一大一小，构成葫芦状。核蛋白体与蛋白质合成有亲密关系，是氨基酸根据与蛋白质合成有亲密关系，是氨基酸根据mBNAmBNA中的遗传密码顺序构成多肽的场所。合成内用蛋中的遗传密码顺序构成多肽的场所。合成内用蛋白质多的细胞，游离的核蛋白体丰富，如幼稚细白质多的细胞，游离的核蛋白体丰富，如幼稚细胞或胚胎细胞。合成外用蛋白质多的细胞，那么胞或胚胎细胞。合成外用蛋白质多的细胞，那么粗面内质网丰富，例如肝细胞、胰腺泡细胞及浆粗面内质网丰富，例如肝细胞、胰腺泡细胞及