异质性细胞器.ppt

异质性细胞器 Still waters run deep.流静水深流静水深,人静心深人静心深 Where there is life,there is hope。有生命必有希望。有生命必有希望Characteristics of LysosomesLysosome is a Lysosome is a heterogenous heterogenous organelleorganelle（异质（异质（异质（异质性细胞器）性细胞器）性细胞器）性细胞器）:1.1.Primary Primary lysosomelysosome（初级（初级（初级（初级溶酶体）溶酶体）溶酶体）溶酶体）2.2.Second Second lysosomeslysosomes（次（次（次（次级溶酶体）级溶酶体）级溶酶体）级溶酶体）3.3.heterophagic heterophagic（异噬溶酶体）（异噬溶酶体）（异噬溶酶体）（异噬溶酶体）1.1.autophagic autophagic（自噬溶酶体）（自噬溶酶体）（自噬溶酶体）（自噬溶酶体）1.1.Residual bodyResidual body（残余小体）（残余小体）（残余小体）（残余小体）Primary LysSecond LysThe Functions of LysosomesvvLysosomes are Lysosomes are involved in three major involved in three major cell functions:cell functions:phagocytosis phagocytosis（吞噬）（吞噬）（吞噬）（吞噬）A summary of the phagocytic pathway autophagy autophagy（自吞）（自吞）（自吞）（自吞）Electron micrograph of a mitochondrion and peroxisome(过氧化物酶体)enclosed in a double membrane wrapper derived from the ER.This autophagic vacuole would have fused with a lysosome and its contents digested.endocytosis endocytosis（内吞（内吞（内吞（内吞作用）作用）作用）作用）Disorders Resulting from Defects in lysosomal FunctionDisorders Resulting from Defects in lysosomal Function I-cell disease:Many cells in these patients contain lysosomes that are bloated with undergraded materials.When fibroblasts from these patients were studied in culture,it was found that lysosomal enzymes are synthesized at normal levels but are secreted into the medium and not targeted to lysosomes.The I-cell defect was soon traced to the deficiency of an enzyme(N-acetyglucosamine phosphotransferase)required for mannose phosphorylation.The secreted enzymes lacked the mannose phosphate residue that are present on the corresponding enzymes of cells from normal individuals.Pompe disease:a fatal inherited conditiona fatal inherited condition in the absence of-glucosidase,undigested glycogen in the absence of-glucosidase,undigested glycogen accumulated in lysosomes,causing swelling of the accumulated in lysosomes,causing swelling of the organelles and irreversible damage to the cells and organelles and irreversible damage to the cells and tissuestissuesDiseases of this type,characterized by the deficiency of a Diseases of this type,characterized by the deficiency of a single lysosomal enzyme and the corresponding single lysosomal enzyme and the corresponding accumulation of undergraded substrate,are called accumulation of undergraded substrate,are called lysosomal storage diseaseslysosomal storage diseasesOther lysosomal storage diseasesDiseaseDiseaseEnzyme Enzyme DeficiencyDeficiencyPrinciple Storage Principle Storage substancesubstanceconsequencesconsequencesGGM1M1 Gangliosid-Gangliosid-osisosisGM1-GM1-GalactosidaseGalactosidaseGanglioside GGanglioside GM1M1Mental retardation,liver Mental retardation,liver enlargement,skeletal enlargement,skeletal involvement,death by age 2 involvement,death by age 2 Tay-Sachs Tay-Sachs dieasedieaseHexosaminidasHexosaminidase Ae AGanglioside GGanglioside GM2M2Mental retardation,blindness,death Mental retardation,blindness,death by age 3by age 3Fabrys Fabrys diseasedisease-Galactosidase Galactosidase A ATrihexosylceramiTrihexosylceramidedeSkin rash,kidney failure,pain in Skin rash,kidney failure,pain in lower extremitieslower extremitiesSandhoffsdisSandhoffsdiseaseeaseHexosaminidasHexosaminidase A and Be A and BGanglioside GGanglioside GM2 M2 and globosideand globosideSimilar to Tay-Sachs diease but Similar to Tay-Sachs diease but more rapidly progressingmore rapidly progressingGauchers Gauchers diseasediseaseGlucocerebrosiGlucocerebrosidasedaseGlucocerebrosideGlucocerebrosideLiver and spleen Liver and spleen enlargement,erosion of long enlargement,erosion of long bones,mental retardation in bones,mental retardation in infantile form onlyinfantile form onlyTay-Sachs disease:the best studied lysosomal the best studied lysosomal storage diseasesstorage diseases It results from a deficiency of the enzyme-N-It results from a deficiency of the enzyme-N-hexosaminidase A,an enzyme that degrades the ganglioside hexosaminidase A,an enzyme that degrades the ganglioside GGM2M2 G GM2M2 is a major component of the membranes of brain cells is a major component of the membranes of brain cells,and in the absence of the hydrolytic enzyme,the ganglioside,and in the absence of the hydrolytic enzyme,the ganglioside accumulates in the bloated lysosomes of brain cells,causing accumulates in the bloated lysosomes of brain cells,causing dysfunctiondysfunction In its severe form,which strikes during infancy,the disease In its severe form,which strikes during infancy,the disease is chacterized by progressive mental and motor retardation,is chacterized by progressive mental and motor retardation,as well as skeletal,cardiac,and resiratory abnormalitiesas well as skeletal,cardiac,and resiratory abnormalities