异质性细胞器精品文稿.ppt

异质性细胞器第1 页，本讲稿共10 页Characteristics of LysosomesLysosome is a Lysosome is a heterogenous heterogenous organelle organelle（异质性细（异质性细胞器）胞器）:l l Primary lysosome Primary lysosome（初级溶酶体）（初级溶酶体）l l Second lysosomes Second lysosomes（次级溶酶体）（次级溶酶体）l l heterophagic heterophagic（异噬溶酶体）（异噬溶酶体）l l autophagic autophagic（自噬溶酶体）（自噬溶酶体）l l Residual body Residual body（残余小体）（残余小体）Primary LysSecond Lys第2 页，本讲稿共10 页The Functions of Lysosomesv v Lysosomes are involved Lysosomes are involved in three major cell in three major cell functions:functions:phagocytosis phagocytosis（吞噬）（吞噬）A summary of the phagocytic pathway第3 页，本讲稿共10 页 autophagyautophagy（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.第4 页，本讲稿共10 页 endocytosisendocytosis（内吞（内吞作用）作用）第5 页，本讲稿共10 页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.第6 页，本讲稿共10 页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.第7 页，本讲稿共10 页Pompe disease:a fatal inherited condition a 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 tissues organelles and irreversible damage to the cells and tissuesDiseases of this type,characterized by the deficiency of a single Diseases of this type,characterized by the deficiency of a single lysosomal enzyme and the corresponding accumulation of lysosomal enzyme and the corresponding accumulation of undergraded substrate,are called undergraded substrate,are called lysosomal storage diseases lysosomal storage diseases第8 页，本讲稿共10 页Other lysosomal storage diseasesDisease Disease Enzyme Enzyme Deficiency DeficiencyPrinciple Storage Principle Storage substance substanceconsequences consequencesG GM1 M1 Gangliosid-Gangliosid-osis osisGM1-GM1-Galactosidase GalactosidaseGanglioside G Ganglioside GM1 M1 Mental retardation,liver Mental retardation,liver enlargement,skeletal enlargement,skeletal involvement,death by age 2 involvement,death by age 2 Tay-Sachs Tay-Sachs diease dieaseHexosaminidas Hexosaminidase A e AGanglioside G Ganglioside GM2 M2 Mental retardation,blindness,death Mental retardation,blindness,death by age 3 by age 3Fabrys Fabrys disease disease-Galactosidase Galactosidase A ATrihexosylcerami Trihexosylceramide deSkin rash,kidney failure,pain in Skin rash,kidney failure,pain in lower extremities lower extremitiesSandhoffsdis Sandhoffsdisease easeHexosaminidas Hexosaminidase A and B e A and BGanglioside G Ganglioside GM2 M2 and globoside and globosideSimilar to Tay-Sachs diease but Similar to Tay-Sachs diease but more rapidly progressing more rapidly progressingGauchers Gauchers disease diseaseGlucocerebrosi Glucocerebrosidase daseGlucocerebroside Glucocerebroside Liver and spleen Liver and spleen enlargement,erosion of long enlargement,erosion of long bones,mental retardation in bones,mental retardation in infantile form only infantile form only第9 页，本讲稿共10 页Tay-Sachs disease:the best studied lysosomal storage the best studied lysosomal storage diseases diseases It results from a deficiency of the enzyme-N-hexosaminidase A,an It results from a deficiency of the enzyme-N-hexosaminidase A,an enzyme that degrades the ganglioside G enzyme that degrades the ganglioside GM2 M2 G GM2 M2 is a major component of the membranes of brain cells,and in the is a major component of the membranes of brain cells,and in the absence of the hydrolytic enzyme,the ganglioside accumulates in the absence of the hydrolytic enzyme,the ganglioside accumulates in the bloated lysosomes of brain cells,causing dysfunction bloated lysosomes of brain cells,causing dysfunction In its severe form,which strikes during infancy,the disease is In its severe form,which strikes during infancy,the disease is chacterized by progressive mental and motor retardation,as well as chacterized by progressive mental and motor retardation,as well as skeletal,cardiac,and resiratory abnormalities skeletal,cardiac,and resiratory abnormalities 第10 页，本讲稿共10 页