Disorders Resulting from Defeats in Lysosomal Function

Other lysosomal storage diseases DiseaseEnzyme Deficiency Principle Storage substance consequences G M1 Gangliosid -osis GM1 β- Galactosidase Ganglioside G M1 Mental retardation,liver enlargement,skeletal involvement,death by age 2 Tay-Sachs diease Hexosaminidase AGanglioside G M2 Mental retardation,blindness,death by age 3 Gaucher’ s disease Glucocerebrosi- dase Glucocerebrosi- de Liver and spleen enlargement,erosion of long bones,mental retardation in infantile form only Fabry’s disease α-Galactosidase A Trihexosylceram ide Skin rash,kidney failure,pain in lower extremities Sandhoff’s disease Hexosaminidase A and B Ganglioside G M2 and globoside Similar to Tay-Sachs diease but more rapidly progressing

Disease: Gaucher’s disease Enzyme Deficiency: Glucocerebrosidase ( 葡糖脑苷脂酶 ) Principal Storage Substance: Glucocerebroside ( 葡糖脑苷脂 ) Consequences: Liver and spleen （脾） enlargement,erosion of long bones,mental retardation （迟缓） in infantile form only

If the victims of this disease have been successfully treated ? yes How? The scientists tell us by enzyme replacement therapy

Treated the enzyme with three different glycosidases （糖苷酶） Exposed underlying mannose residues （甘露糖残基） Recognized by mannose receptors on the surface of macrophages （巨噬细胞） Taken up by receptormediated endocytosis （受体介导的胞吞作 用） Delivered the enzymes to the lysosomes

Disease: Fabry’s disease Enzyme Deficiency: Principal Storage Substance: Consequences: α-Galactosidase A 半乳糖苷酶 Trihexosylceramide （） Skin rash （疹）,kidney failure,pain in lower extremities （四肢）

Many patients with lysosomal storage diseases carry a mutation that destabilizes the encoded enzyme and causes it to misfold. Now, the scientists have found a good way to treat the patients This misfolded proteins are recognized and destroyed,which is the reason these individuals lack the enzyme.

Any competitive inhibitors （抑制 剂 ） of the enzyme α – galactosidase A (for example Galactose) Bind to the enzyme’s active site and hold the mutant enzyme in a native-like structure that enables it to avoid destruction in the ER Departed the ER and transported to lysosomes