Disorders Resulting
from Defects in
Lysosomal Function
Characteristics of Lysosomes
Lysosome is a
heterogenous
organelle（异质
性细胞器）:
Primary
lysosome（初级
溶酶体）
Second
lysosomes（次
级溶酶体）
heterophagic
（异噬溶酶体）
autophagic
（自噬溶酶体）
Residual body
（残余小体）
Primary Lys
Second Lys
The Functions of Lysosomes
 Lysosomes are
involved in three major
cell functions:
① phagocytosis（吞噬）
A summary of the
phagocytic pathway
② autophagy（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.
③ endocytosis（内吞
作用）
Disorders 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 o
an enzyme(Nacetyglucosamine
phosphotransferas
e)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 condition
in the absence ofα-glucosidase ,undigested glycogen
accumulated in lysosomes,causing swelling of the
organelles and irreversible damage to the cells and
tissues
Diseases of this type, characterized by the deficiency of a
single lysosomal enzyme and the corresponding
accumulation of undergraded substrate,are called
lysosomal storage diseases
Other lysosomal storage diseases
Disease
Enzyme
Deficiency
Principle Storage
substance
consequences
GM1
Gangliosidosis
GM1 βGalactosidase
Ganglioside GM1
Mental retardation,liver
enlargement,skeletal
involvement,death by age 2
Tay-Sachs
diease
Hexosaminidas
eA
Ganglioside GM2
Mental retardation,blindness,death
by age 3
Fabry’s
disease
αGalactosidase
A
Trihexosylcerami
de
Skin rash,kidney failure,pain in
lower extremities
Sandhoff’sdis
ease
Hexosaminidas
e A and B
Ganglioside GM2
and globoside
Similar to Tay-Sachs diease but
more rapidly progressing
Gaucher’s
disease
Glucocerebrosi
dase
Glucocerebroside
Liver and spleen
enlargement,erosion of long
bones,mental retardation in
infantile form only
Tay-Sachs disease: the best –studied lysosomal
storage diseases
It results from a deficiency of the enzyme β-Nhexosaminidase A, an enzyme that degrades the ganglioside
GM2
GM2 is a major component of the membranes of brain
cells ,and in the absence of the hydrolytic enzyme ,the
ganglioside accumulates in the bloated lysosomes of brain
cells,causing dysfunction
In its severe form ,which strikes during infancy ,the disease
is chacterized by progressive mental and motor retardation,
as well as skeletal ,cardiac,and resiratory abnormalities