细胞器与疾病

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 and is surrounded by a double membrane or

2、 , composed of and .the outer membrane is contiguous with the erthe nuclear membrane contains , which provide selective access into and out of the nuclear lumenthe inner membrane has a protein lining called the nuclear lamina, which binds to chromatin and other nuclear components. continuous aqueous

3、 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 called transporter functions to move molecules through pore. there is a ring of proteins that anchors pore

4、 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 transcribed and ribosomal subunits are assembledhttp:/ of dna with rrna genes nucleolar organizing reg

5、ion = (nor) ribosomal proteins are synthesized in cytoplasm and transported into the nucleusthese proteins self associate with appropriate rrna during rrna synthesis forming immature ribosomal subunitsribosomes finish self assembly in cytoplasm endoplasmic reticulumkedlr-gfp激光共聚焦显微镜下的erthe endoplasm

6、in reticulum (er) is an extensive, extra-nuclear membrane system with the following functions:er is a home for various enzymes involved in protein folding , drug detoxification, membrane lipid biosynthesis, cholesterol and fatty acid metabolismer is an entry point for protein sorting. targeting of t

7、hese proteins is mediated by signal sequence. the membrane proteins are inserted into the er membrane in their proper orientation. secreted proteins are translocated into er lumen and then transported to the destination place rough and smooth ertwo regions of the er differ in both structure and func

8、tion. rough er has ribosomes attached to the cytoplasmic side of the membrane. smooth er lacks attached ribosomes. typically, the smooth er is a tubule network and the rough er is a series of flattened sacs.:8001/esgbio/cb/org/er.gifthe smooth er has a wide range of functions in

9、cluding carbohydrate and lipid synthesis. it serves as a transitional area for vesicles that transport er products to various destinations. in liver cells the smooth er produces enzymes that help to detoxify certain compounds. in muscles the smooth er assists in the contraction of muscle cells and i

10、n brain cells it synthesizes male and female hormones. the rough er manufactures membranes and secretory proteins the rough and smooth er areusually interconnected and the proteinsand membranes made by the rough er move into the smooth er to be transferred to other locations. the cytoplasm has a red

11、ucing environment, while er lumen is oxidizing . this difference is generated by unequal distribution of trypeptide glutathione and is essential for formation of disulfide 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

12、: mitochondrion) are the sites of aerobic respiration, and generally are the major energy production center in eukaryotesthe number of mitochondria range from one to thousands per cells.they are often positioned in cells nearest to sites of energy utilizationone of the richest sources of mitochondri

13、a 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 fairly simple phospholipid bilayer, containing porins, proteins that render it permeable to molecules of about 10 kilodaltons or less. ions

14、, nutrient molecules, atp, adp, etc. easily pass through the outer membrane and enter the intermembrane space the inner membrane is more complex and contains respiratory chains and transportersthe matrix lies within the inner membrane. the access to this compartment often requires specific transport

15、ersfour possible localization for mitochondrial enzymeslocated near cell nucleus, consists of flattened, membrane-bounded sacs (cisternae) forming a stackeach stack has:cis-face is an entry face - adjacent to er to accept incoming vesiclestrans-face is an exit face points towards plasma membrane, pr

16、oduces 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 mannose,phosphorylationmedial removal of mannose, addition of n-acetylglucosaminetrans removal of galactose, addition of sialic acidtgn addit

17、ion of sialic acid, sortingcisternae segregated into convex (cis), medial (middle), and concave (trans) compartments.ercysmedialtranstgngolgi structure/function/-related diseasesgolgi and mitosisgolgi and apoptosisgolgi and liver cancerhne induces golgi fragmentscontrol30 min1 h2 h4 hlysosomes1、初级溶酶

18、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，是高尔基体分泌形成的（如右图）。分泌形成的（如右图）。含有多种水解酶，但没含有多种水解酶，但没有活性，只有当溶酶体有活性，只有当溶酶体破裂，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，已知酶、磷脂酶类，已知60余种，这些酶均属于酸余种，这些酶均属于酸性水解酶，反应的最适性水解酶，反应的最适ph值为值为5左右，溶酶体左右，溶酶体膜虽然与质膜厚度相近

19、，膜虽然与质膜厚度相近，但成分不同但成分不同，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，正在进行或完成消化作在进行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

20、故名，残体可通残渣故名，残体可通过外排作用排出细胞，过外排作用排出细胞，也可能留在细胞内逐也可能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）。lysosomes are active in recycling the cells organic material and in the intracellular digestion of macromolecules. lysosomes contain various hydrolytic enzymes that are capable of digesting nucleic acids, pol

21、ysaccharides, fats and proteins.the inside of a lysosome is acidic. in humans, a variety of inherited conditions can affect lysosomes. these defects are called storage diseases. people with these disorders are missing one or more of the lysosomal hydrolytic enzymes. 动物细胞溶酶体系统示意图 lysosome-related dis

22、eases 溶酶体酶缺失或溶酶体酶的代谢环节故障，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殖（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形成氢键，导致吞噬细胞溶酶体崩解，细胞本身也被破坏，矽尘释出，后又被其他巨噬细内吞噬，如此反复进行。受损或已破坏的巨噬细胞释放“致纤

23、维化因子”，并激活成纤维细胞，导致胶原纤维沉积，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 motility. provides machinery for organelle transport, chromas

24、ome 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 in diameter) filaments are dynamic, i.e. they can assem

25、ble 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 the entire volume of the cellwhereas actin fibers are co

26、ncentrated 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 dividing cell/external/frank.gibbo

27、ns/spindle.htmlmicrotubules provide tracks for transport are long hollow cylinders made of tubulinprotofilaments are linear chains of tubulin dimers, a parallel bundle of 13 protofilaments forms a microtubulethere are three kinds of tubulins, each with many subtypes: and form a/b tubulin dimers and

28、represent the basic building block of microtubules 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 from atp. one end of the pro

29、tein 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 movementassociation of actin filaments

30、with myosin can form contractile structures核蛋白体核蛋白体 在粗面内质网表在粗面内质网表面的称固着核蛋白体，面的称固着核蛋白体，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起称多聚体聚集在一起称多聚核蛋白体，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起形蛋白体串连在一起形成。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。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

31、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。两个亚基合在一起时，由于一大一小，形成葫芦状。核蛋白体一起时，由于一大一小，形成葫芦状。核蛋白体与蛋白质合成有密切关系，是氨基酸根据与蛋白质合成有密切关系，是氨基酸根据mbnambna中的遗传密码顺序形成多肽的场所。合成内用蛋中的遗传密码顺序形成多肽的场所。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，则粗胞或胚胎细胞。合成外用蛋白质多的细胞，则粗面内质网丰富，例如肝细胞、胰腺泡细胞及浆细面内质网丰富，例如肝细胞、胰腺泡细胞及浆细胞等。胞等。中心粒中心粒 (centrio1es)中心粒与细胞分裂有关，