家装电工基础知识.ppt

第四节 溶酶体和过氧化物酶体 溶酶体（lysosome）的发现较晚，首先是由Christian de Duve (1955)发现的。 在溶酶体中含有丰富的水解酶，现已知，所有的动物细胞（特化的红细胞除外）内都含有溶酶体；植物细胞中也发现有类似溶酶体的圆球体结构,东莞电工培训 http:/www.px36.com/training-215.html,Plant cell vacuoles.,光镜下的内皮细胞：绿色荧光定位溶酶体 红色显示线粒体,由高尔基复合体成熟面的扁平囊形成有被小泡， 脱落后再与内体合并即为内体性溶酶体。,当内体性溶酶体与细胞内衰老 的细胞器或由细胞胞吞作用摄入 的外来物质融合后便形成吞噬性 溶酶体。,An electron micrograph showing two small lysosomes and one large lysosome. These organelles contain enzymes capable of breaking down various substances.,一 溶酶体的结构类型 L是一种异质性细胞器.根据L的不同生理阶段可分为 (1)初级溶酶体或原溶酶体（primary lysosome）或无活性的溶酶体。 (2) 次级溶酶 体当初级溶酶体与来自细胞外部或细胞内部的物质相互作用时，就称为次级溶酶体（secondary lysosome）。次级溶酶体又有不同的名称，,体与固体物质作用或与吞噬泡相互作用所形成的次级溶酶体又称为吞噬溶酶体（phago lysosome）。如果初级溶酶体与液体物质或胞饮小泡相互作用因此这种次级溶酶体又称为多泡小体(multivesclar body)。次级溶酶体也被称为消化泡。如以被消化的物质是外源或是内源的也可将次级溶酶体分为两种形式，,一种是异体吞噬泡（heterophagic vacuole）,它作用的物质来自于细胞外；一种是自体吞噬泡（autophagic vacuoles），它作用的底物是细胞内的垃圾，如一些细胞器的残片。,初级溶酶体,次级溶酶体,残余小体,A summary of the autophagic pathway.,A summary of the phagocytic pathway .,The endocytic pathway.,(3)在溶酶体内剩下一些不能分解的残渣物质，这时的溶酶体称为残留小体（residual body）或称三级溶酶体(tertiary lysosome）。 残留小体有些可通过外徘作用排出细胞,有些则积累在细胞内不被排出，形成一些固定的细胞内结构。如：脂褐质，常见于神经细胞和心肌细胞之中，为形状不规则，被单位膜包围的小体；其内容物电子密度较高。 老年斑的形成,老年斑的形成,Colorized scanning electron micrograph of a cell ingesting a synthetic particle.,Phagocytosis.,溶酶体膜的特点: (1) 有质子泵,H H H,氢离子浓度比细胞质中高出100倍 H HH,H,H H,(2) 具有多种载体蛋白将水解产物向外运转,(3)膜蛋白高度糖基化,溶酶体的特征酶是酸性磷酸酶. 酶的最适PH是5左右,少量的溶酶体酶泄漏不会造成细胞损伤.主要原因是胞质的PH是7.0左右.,二 溶酶体的功能 1 清除胞内和体内的垃圾 由于溶酶体中含有丰富的水解酶，因此，细胞内许多的分解作用都可以由这些水解酶来完成。把溶酶体在细胞内分解各种物质的过程叫溶酶体的消化作用。因此，溶酶体也是细胞内的“消化器官”。,对于细胞来说，不是所有的物质的分解都通过溶酶体进行的。高等动物组织的细胞，大部分的小分子营养物质是通过细胞膜从血液内吸收进入细胞；一些分子量大的不能直接通过细胞膜的物质，是由内吞作用形成吞噬泡或胞饮泡进入细胞内。进入细胞的大分子物质及外面所包被的膜结构，与初级溶酶体接近并融合，溶酶体内的水解酶开始作用，分解大分子物质成小分子物质，即进行消化作用,2 防御功能 L的防御功能主要体现在几种吞噬泡中.如,位于肝脾等血通道.(1)吞噬清除抗原抗体复合体(2) 吞噬细菌病毒等.(3)机体感染发炎部位巨噬细胞的吞噬作用. 死细胞的清除主要是由巨噬细胞完成.,巨噬细胞的L非常多,L的酶协同过氧化氢等强氧化剂共同作用杀死细菌.由于巨噬细胞较多的吞噬作用,所以也可以看到巨噬细胞中有较多的残余小体.这可能导致巨噬细胞的短寿. 3 L的其他生理功能. (1) 作为消化器官为细胞提供营养 (2) 在分泌腺细胞中,参与分泌过程的调节 如 分泌细胞吞噬储存在腺体内腔的甲状腺球蛋白,吞噬泡与L融合,甲状腺球蛋白被水解成甲状腺素,然后分泌到细胞外的,毛细血管中 (3) 两栖类发育蝌蚪尾巴的退化,(4) 受精作用,精 子 形 成 模 式 图,The acrosomal reaction during sea urchin fertilization,Acrosomal profilacin,The cortical reaction during sea urchin fertilization,三 L的发生,Gol中的磷酸转移酶是如何在ER向G转送众多的蛋白质中识别溶酶体酶蛋白?现在知道溶酶体酶蛋白存在识别信号研究表明这一信号不是一段肽链而是依赖于构象的信号区(signal patch)186。,Secretary lysosome 187 1 granzyme 2 不依赖M6P,Lysosomes in Health and Disease If the cell does not produce a certain lysosomal enzyme or if an enzyme is not properly “addressed“ in the Golgi apparatus, a lysosomal storage disease can result. These diseases are caused by a massive accumulation of material that should have been digested in the lysosome.,The sorting of lysosomal enzymes in a normal cell (left). First, enzymes receive a chemical “address label“ in the Golgi apparatus (a) and move in vesicles (b) to a lysosome (c). Any enzyme that is accidentally swept out of the cell (d) is recaptured and taken back to the lysosome (e). If some part of the process goes awry, a lysosomal storage disorder can result.,For example, in Hurler's syndrome (center), an enzyme is not produced (f), and the lysosome therefore lacks that enzyme (g). If correctly tagged enzyme is added to the cells in test tubes (h), the cells can capture the enzyme and take it to the lysosome (i).,In I-cell disease (right), enzymes are correctly made, but they are not tagged in the Golgi (j), and therefore are not sent to the lysosome. When such enzymes leave the cell (k), they cannot be recaptured (l) and so the lysosome remains empty (m).,小儿致死遗传性疾病-台-萨氏病,神经节苷脂- GM2- 在神经细胞中GM2比较多 在正常情况下GM2的代谢如下:,水解神经节苷脂GM2需要ß氨基己糖脂酶A,水解神经节苷脂GM2D的ß氨基己糖脂酶A缺失,Lysosomal storage disorders.,这样在神经细胞特别是脑细胞中GM2就会积累起来,最后造成精神呆滞,小儿在4-6岁时就会夭折. 这类疾病被称为储积症,共有几十种,是一种隐性的遗传病.,Persons with the lysosomal storage disease known as Hurler's syndrome, for example, cannot break down large molecules of sugar compounds called glycosaminoglycans because their lysosomes do not contain the enzyme iduronidase. Glycosaminoglycans accumulate in the lysosomes, swelling them so much that the functioning of the entire cell is impaired.,Hurler's syndrome also called GARGOYLISM, ,脂质软骨营养障碍 OR MUCOPOLYSACCHARIDOSIS I,黏多糖(贮积)病(指任何一种涉及黏多糖先天性代谢紊乱的疾病) one of several rare genetic disorders involving a defect in the metabolism of mucopolysaccharides, the class of polysaccharides ，that bind water to unite cells and to lubricate joints.,Onset of the syndrome is in infancy or early childhood, and the disease occurs with equal frequency in both sexes. Affected individuals exhibit severe mental retardation, clouding of the corners of the eyes, deafness, hirsutism (hairiness), enlarged liver and spleen, dwarfism with hunched back, short limbs and clawed hands,a large head with wide-set eyes, heavy brow ridges and deep bridge of nose, and poorly formed teeth. The disorder is identifiable within two years of birth; such children require institutional care and usually do not live beyond adolescence. Death most often results from heart failure, which is attributable to infiltration of heart muscle and coronary vessels with mucopolysaccharides.,A particularly severe lysosomal disorder is known as I-cell disease. Children born with this disease lack the entire range of lysosomal enzymes. The enzymes are made, but they are dumped outside the cell instead of being sent to the lysosomes.,Various cellular nutrients thus cannot be digested and so pile up in dark lumps, called inclusion bodies, within the lysosomes. The disease affects the kidneys, heart, and nervous system, and children with it usually die of heart failure or pneumonia before reaching puberty.,In the early 1970's, Elizabeth Neufeld, who was then at the National Institutes of Health, showed that the lysosomal enzymes of persons with I-cell disease emerge from the Golgi apparatus without the chemical tag they need to be directed to the lysosomes. She also showed that the defect could be corrected in test-tube cultures of cells taken from people with the disease. The corrective factors she supplied were the specific, properly tagged enzymes that the cells lacked.,Although enzyme replacement therapy is not being used to treat people with lysosomal storage diseases like Hurler's syndrome, it is being used to treat a different group of disorders called lipid storage diseases. Enzyme replacement therapy for many disorders presents challenges to researchers, however, because purified enzymes injected directly into the body tend to be quickly destroyed or inactivated.,It is particularly difficult to get enzymes into brain cells-an important problem now under investigation, since several lysosomal storage diseases produce severe mental retardation.,四 过氧化物酶体 微体或过氧化氢体 （peroxisome） 一、微体由单层膜包围，中有一些中等致密度的颗 粒状物质和结晶状结构的囊状小体，所含物质主要 有过氧化氢酶和其它一些氧化酶。 二、功能：解毒作用,微体 在植物细胞称园球体 乙醛酸循环体为微体 1. 过氧化物酶体和溶酶体的区别P189 2.过氧化物酶体的功能 (1) 解除过氧化氢的毒害,氧化酶 过氧化氢酶 O² O² H²O² 2H²O RH ² R H²O² (2) 分解脂肪酸为细胞提供热量 (3) 在植物细胞中的作用,The structure and function of peroxisomes.,3 peroxisomes的发生 190,