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5	二、细胞质基质的某些物理特性     液晶态,生理状况不同,黏性和液体性随之变化,有弹性。
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7	第三节  细胞质基质的功能 内外物质交换的控制； 维持细胞的完整性提供离子环境及行使功能所需要的底物； 胚胎发育时，对细胞分化发挥重要作用； 生化反应的场所。
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17	Endoplasmic Reticulum Consists of a continuous network of flattened sacs, tubules, and vesicles throughout cell cytoplasm. Each sac is called a cisterna (cisternae).池 Space enclosed in the ER lumen.腔
18	"Responsible for synthesis of proteins..." Responsible for synthesis of proteins that are incorporated into ER, Golgi, endosomes, lysosomes, cell membrane Also responsible for synthesis of proteins secreted by the cell Also involved in biosynthesis of lipids, including triacylglycerols(三酰〔基〕甘油), cholesterol.
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23	"Are different morphologically" Are different morphologically: RER forms flattened sheets SER forms tubular structures Both are present in eukaryotic cells, but relative amounts vary Those that secrete a lot of proteins have more RER Those that produce steroid hormones have more SER
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25	内质网的功能 粗面内质网：蛋白质的合成、折叠与转运，蛋白质的糖基化。 滑面内质网：小分子物质（脂类）的合成与代谢、储存和调节钙离子浓度以及细胞的解毒作用等。
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29	Endomembrane and secreted proteins Signal recognition particle (SRP) binds signal sequence  --> blocks translation SRP binds SRP receptor Ribosome binds ribosome receptor Polypeptide moves into pore
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31	Endomembrane and secreted proteins GTP hydrolysed --> SRP released Translation continues;  polypeptide transported through pore protein
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33	Endomembrane and secreted proteins Signal sequence remains bound to pore protein Signal sequence cleaved by signal peptidase Polypeptide released in ER lumen
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37	Function of Rough Endoplasmic Reticulum（2） Involved in biosynthesis and processing of proteins. Specifically, RER is involved in synthesis of transmembrane and soluble proteins. These proteins can be incorporated into organelles of endomembrane system, incorporated into cell membrane, or exported from cell
38	Function of Rough Endoplasmic Reticulum（3） Most proteins that enter ER are inserted into ER lumen cotranslationally, as ribosome synthesizes protein. Soluble proteins are released into ER lumen. Only a small number of proteins are imported postranslationally, after synthesis. True for peroxisomes, chloroplasts, and mitochondria
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40	蛋白质的折叠
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46	Function of Rough Endoplasmic Reticulum（4） RER is also site for: Addition of carbohydrate groups called glycosylation Folding of polypeptides Assembly of multimeric proteins Quality control
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52	Lipid Biosynthesis of the ER membrane, the layer exposed to cytosol Enzymes that synthesize lipids are cytosolic Flippases transfer membrane lipids ER is primary source of membrane lipids Restricted to one monolayer to other monolayer Flippases are found for phosphatidylcholine, but not phosphatidylethanolamine, phosphatidylserine, or phosphatidylinositol Only phosphatidylcholine can appear in both monolayers
53	Lipid Biosynthesis Membrane components transferred to chloroplast and mitochondrial membranes by phospholipid exchange proteins Carries lipid through the cytosol to another membrane Contributes to movement of phospholipids to other cellular organelles, including cell membrane.
54	2.药物代谢与解毒
55	Drug Detoxification Common reaction is hydroxylation(羟化), addition of hydroxyl groups to organic molecules Depends upon cytochrome P-450, found in smooth ER of liver cells Use NADH or NADPH as electron donor as in following reaction:        RH + NADPH + H+ + O2 ----->                ROH + NADP+ + H20
56	Drug Detoxification(2) Enzymes that catalyze these reactions are called mixed-function oxidases or monooxygenases In drug detoxification(解毒), addition of -OH increases solubility in water Can be easily flushed (发红,冲洗) from body in blood and urine
57	Aryl Hydrocarbon Hydroxylase Another enzyme found in smooth ER Part of this enzyme is cytochrome P-448 Responsible for hydroxylating polycyclic hydrocarbons Often causes products to be more toxic than reactants(反应物) Enzyme can also convert potential carcinogens into active forms
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59	"糖原的分解也有ER的参与..." 糖原的分解也有ER的参与。肝细胞内的SER朝向细胞质基质的膜面附着的糖原颗粒，可被磷酸化酶降解，形成1-磷酸葡萄糖，再在细胞质基质中转化为6-磷酸葡萄糖。然后，再由SER上的1-磷酸葡萄糖酶将6-磷酸葡萄糖的磷酸根脱掉，把葡萄糖转移到ER腔中，然后再释放到血液中，供给细胞完成多种生理功能。
60	Carbohydrate Metabolism Contains glucose 6-phosphatase, which removes phosphate group from glucose 6-phosphate to form free glucose from glycogen Already talked about glycogen degradation Reaction must occur because membranes are impermeable(不透性) to phosphorylated sugars
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62	4.储存和调节Ca2+浓度(Calcium Storage)
63	"ER lumen can contain high..." ER lumen can contain high concentrations of calcium-binding proteins Also have ATP-dependent calcium pumps Help keep calcium levels low in a cell
64	五、内质网的病理性变化 ER是一个比较敏感的细胞器。 内质网肿胀：ER膨大成空泡状，电子密度底于正常，伴有线粒体肿胀，病理学上称为浊肿（cloudy sweelling）。缺氧、辐射等。 内质网脱粒：药物中毒、病毒感染等。 内质网内包涵体：某些疾病中可看到脂类、蛋白质在ER腔中积累。如脂肪肝细胞中有大量脂质体存在；肝硬化患者的肝细胞可见到ER腔中聚集大量的α1-AT。
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69	大囊泡trans Golgi network）  φ 100-500nm; 膜厚：8nm; 泡内含物质：高电子密度物质，浓缩泡。 来源：扁平囊周边或局部球状膨突脱落形成。
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71	扁平囊（medial Golgi network） 呈盘状，3-10层称高尔基堆 扁平囊间距：20-30nm； 囊腔宽：6-15nm 凸  面：形成（顺）面； 凹面：成熟（反）面 形成面膜厚： 6nm; 成熟面膜厚：8nm 囊腔内含：中等电子密度的物质 来        源：小囊泡融合。
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73	小囊泡（cis Golgi network）  φ30-80nm球形小泡 膜厚：6nm; 泡内含物质：低电子密度物质，较透明。 来源：由rER‘芽生’而来。
74	Structure of Golgi Complex Consists of flattened membrane-bounded cisternae Usually 3-8 cisternae(池) per stack Number and size depend upon metabolic activity of the cell Transport from one cisterna to another is by transport vesicles
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80	"高尔基复合体在细胞分泌活动..."          高尔基复合体在细胞分泌活动中起着重要的运输作用；在分泌颗粒的形成过程中起着浓缩、修饰、加工等作用。
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83	N-linked Glycosylation Can be further divided into two stages: Initial glycosylation event Subsequent modification of the carbohydrate side chain
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85	Protein Glycosylation Defined as the addition of carbohydrate groups to specific amino acid residues in a protein
86	"There are two kinds of..." There are two kinds of glycosylation: N-linked -addition of carbohydrates to asparagine residues O-linked - addition of carbohydrates to serine or threonine residues
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90	（三）高尔基复合体对蛋白质的分拣运输
91	Protein Sorting Proteins must be directed to a variety of organelles. Once it arrives, there must be a mechansim to prevent it from leaving Each protein has a “tag” that targets protein for a particular organelle Tag is usually an amino acid sequence, an oligosaccharide side chain, or a hydrophobic domain
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93	（五）高尔基复合体与膜的转变 内质网
94	Golgi Complex Plays significant roles in: Chemical modification of proteins Sorting of proteins Packaging of proteins
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102	Lysosomes Contain digestive enzymes capable of degrading all major classes of macromolecules Used to degrade(降解) materials brought into cell and intracellular structures and macromolecules no longer needed or damaged
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106	Development of Lysosomes   Enzymes are synthesized by ribosomes on RER, transported to Golgi where they are tagged with mannose (甘露糖) 6-phosphate, sorted for transport Late endosome is an unused lysosome
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113	Autophagy Breaks down cellular structures and components damaged or no longer needed Seen in RBCs, which digest all internal organelles. Seen in starved cells as a desperate attempt to continue to provide energy needs of the rest of the cell.
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115	溶酶体参与免疫过程  抗原被巨噬细胞吞噬和处理(溶酶体参与)，使抗原物质保留下来，然后再将这免疫信息传递(携带或释放抗原)给T/B淋巴细胞，使他们分泌淋巴素或抗体。        免疫过程中形成的抗原抗体复合物（正常情况下被吞噬），在炎症或损伤时，可促使溶酶体释放中性蛋白酶，破坏血管的弹性蛋白而致脉管炎，破坏肾小球微血管基质引起肾小球肾炎，破坏肺的结缔组织而致肺气肿，破坏软骨而致关节炎。
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117	溶酶体参与受精过程  当精子与卵外层膜接触后，形成小孔道，顶体内的各种酶（顶体酶）便被激发而释放到细胞外，称顶体反应（acrosome reaction）。透明质酸梅使精子穿过卵丘的细胞层；放射冠穿透酶使精子冲破放射冠抵达透明带；而顶体素使精子突破透明带抵达卵黄膜；最后在一种尚不清楚的酶的作用下使精子入卵（产生抑制顶体素物质，封闭透明带，使其他精子不易进入卵）。
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120	"参与细胞内激素的降解：一些..." 参与细胞内激素的降解：一些激素并不全部释放，降解量可占激素（肽类）的15-50%， 参与膜循环：质膜—有/无被小泡—内吞体—溶酶体或多泡体—高尔基复合体—分泌泡—质膜
121	Extracellular Digestion Lysomes discharge contents outside the cell by exocytosis Examples: Sperm release of enzymes from acrosome to digest egg membrane Rheumatoid arthritis - release of lysosomal enzymes into joints Steroid hormones cortisone(可的松) and hydrocortisone thought to work by inhibiting lysosomal enzyme release Potent (有效的) antiinflammatory drugs
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124	Lysosomal Storage Diseases Characterized by harmful accumulation of specific substances Happens because enzymes are defective or missing Most are not yet treatable Examples: Hurler disease Hunter syndrome Tay-Sachs disease
125	Hurler Disease Result of a defect in degradation of glycosaminoglycans Defective enzyme is a-L-iduronidase Sweat gland cells of these patients filled with atypical vacuoles
126	Tay-Sachs Disease Results from accumulation of gangliosides(神经节苷脂) in nervous tissue                                  (乙酰己糖胺酶) Missing enzyme is b-N-acetylhexosaminidase Symptoms include mental retardation, paralysis, and death within three years
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134	Peroxisomes Also bounded by a single membrane About 50 matrix enzymes 100 – 1000 peroxisomes per cell Like the lysosome, the peroxisome is a cellular ecosystem, this time basic, pH 8.3 Prominent(突／杰出的) organelle in mammalian kidney and liver cells Defining characteristic is presence of catalase, which degrades hydrogen peroxide produced by organelle metabolism
135	Other Roles for Peroxisomes Detoxification of harmful compounds Oxidation of fatty acids - b-oxidation of fatty acids to acetyl CoA Metabolism of nitrogen(氮)-containing compounds Done during purine catabolism Transaminations - used to remove amino group from amino acids for catabolism Catabolism of unusual substances Contain enzymes that break down xenobiotics(异物), such as alkanes(烷属烃)
136	Peroxisomal Disorders Most common peroxisomal disorder is X-linked adrenoleukodystrophy(肾上腺脑白质营养不良) Defective protein may be involved in transporting long-chain fatty acids  into peroxisome for b-oxidation Causes long chain fatty acids to accumulate in myelin(髓鞘质) sheath (鞘) of nervous tissue
137	Endomembrane System System of membranes within cell across which proteins and lipids are transported and distributed Shuttling between compartments is done via transport vesicles that contain soluble cargo Also part of the vesicle are the membrane proteins and lipids that come as part of the vesicle’s membrane
138	第五节  内膜系统与细胞内的房室化 一、细胞内的房室化
139	第五节  内膜系统与细胞内的房室化
140	"后来先后证明了分选信号..." 后来先后证明了分选信号、信号识别颗粒(signal recognition particle，SRP)及其受体及细胞膜上的蛋白质传导通道（protein-conducting channel,PCC）的存在，使信号假说成为一个系统的理论。信号假说不仅正确，而且具有普遍性，真核细胞合成的新生肽链上都存在有分选信号。
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142	Signal recognition particle (SRP) Brings protein to ER Binds signal sequence on protein Binds SRP receptor on ER RNA-protein complex
143	Integral membrane proteins Start transfer sequence binds SRP and anchors polypeptide in membrane N-terminus in cytosol C-terminus in ER lumen
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147	Integral membrane proteins Stop transfer sequence stops translocation through membrane: anchors polypeptide N-terminus in ER lumen C-terminus in cytosol
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152	Targeting to nucleus review Translated in cytoplasm Nuclear localization signal (NLS) required for transport through nuclear pore
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163	第五节  内膜系统与细胞内的房室化 门孔运输:定位于细胞核的蛋白质是通过核膜上的核孔复合体(nuclear pore complex, NPC)进入细胞核。 跨膜运输：定位于线粒体、过氧化物酶体、内质网的蛋白质是通过这些细胞器膜上的蛋白质通道进入细胞器。信号肽引导入后，信号肽被切除。解折叠通过蛋白伴侣来完成。
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165	Vesicular Trafficking Sorting begins in ER and Golgi complex Contain mechanisms for retrieving（回收） or retaining compartment-specific proteins Helps to maintain the integrity of the glycosylation and processing pathways Final sorting takes place in Golgi, the trans-Golgi network Proteins are packaged for shipment to various organelles
166	第六节  内膜系统与膜流 膜流（membrane flow）:是指细胞的膜成分在质膜与内膜之间，以及在内膜系统各种结构之间流动的现象。又称为小泡流（vesicle flow)。 膜流过程中，提供膜性小泡的膜结构成为供体房室(donor compartment)或供体膜，接受膜性小泡的膜结构成为受体房室(acceptor c.)或受体膜。膜的再循环(membrane recycling)实现细胞器膜成分的内在平衡机制(homeostatic mechanisms)。
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169	Secreted proteins         Proteins move from Golgi complex to plasma membrane in secretory vesicles
170	Secretory Pathways Two modes of secretion by eukaryotic cells: Constitutive - continuous discharge of proteins Regulated - controlled, rapid release of proteins in response to extracellular ligand
171	Constitutive Secretion After budding from trans-Golgi network, vesicles move directly to membrane Release contents extracellularly Occurs in most eukaryotic cells
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173	Regulated Secretion Used by few eukaryotic cells Secretory vesicles accumulate in cytosol until there is a specific signal to cause them to move to cell membrane Contents are concentrated by condensation Vesicles then move to membrane and wait for signal to be released by exocytosis
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188	第七节  内膜系统的起源 内质网：构成膜结构的脂类和蛋白质大都是在ER合成，ER是生物膜发生的主要场所。 SER来自RER（超微结构相连；生化－许多膜蛋白相同；药物先RER后SER）：脱去核糖体或从没有核糖体部分生长出来； SER和RER独立发生。 高尔基复合体：有其它模转变来；起源于核膜。 溶酶体：RER →高尔基复合体→溶酶体。 过氧化物酶体：SER→高尔基复合体（或RER）→过氧化物酶体
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204	Endomembrane System Review Interconnected system of membrane compartments Nuclear envelope ER Golgi complex Lysosomes Secretory vesicles Plasma membrane
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210	ER-specific Proteins Composition of ER maintained by preventing proteins from escaping and retrieving those that do leave ER-resident proteins contain the amino acid sequence (KDEL; Lys-Asp-Glu-Leu). When this protein binds to a specific receptor in cis-Golgi network, it is packaged in a vesicle and returned
211	Golgi-specific Proteins Some Golgi-resident proteins contain amino acid sequences that serve as tags for retention or retrieval. Another mechanism may also be important. All known Golgi-resident proteins are transmembrane proteins Width of Golgi membrane stacks increases as move from cis- to trans-Golgi network
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213	Soluble Proteins These proteins move from ER to early compartments of Golgi while undergoing glycosylation In Golgi, the mannose residues are phosphorylated Oligosacharide tag is specific for lysosomal proteins Late endosomes then fuse with vesicles carrying materials for digestion
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215	I-cell Disease A lysosomal storage disease caused by absence of mannose 6-phosphate molecules on proteins destined for lysosomes Due to defective phosphotransferase, which catalyzes addition of GlcNAc-1-phosphate to mannose residues Proteins are not properly tagged for delivery to lysosomes