(Solved ) USMLE Lysosomal Storage Diseases:
Questions & Answers: Updated
Lysosomes are primarily produced from the ____ and become secondary lysosomes
only after ____ with other vesicles (autophagosomes) - ANSWERgolgi apparatus;
fusion
Lysosomes break down large molecules taken into the cell by endocytosis to basic
molecular parts for ____ or ____ into new structures - ANSWERenergy production or
recycling
There are different functions of lysosomes for different materials -
ANSWERproteolytic enzymes, lipolytic enzymes, carbohydrate hydrolyzing enzymes,
nucleic acid hydrolyzing enzymes
Enzyme trafficking to lysosomes (4 steps) - ANSWER1. Lysosomal enzymes are in
inactive form (zymogen) in the ER
2. Post-transitionally modified with Mannose-6-Phosphate
3. Transported from golgi to lysosomes
4. activated in lysosomes by LOW pH
Why are lysosomal enzymes inactivated at first? - ANSWERbecause if not, they
would degrade everything around it (until getting to the right place)
What are lysosomal enzymes activated by ___? - ANSWERlow pH
While in the ER, lysosomal enzymes are also modified by ____. This requires -
ANSWERN-linked glycosylation; Asparagine/Serine/Threonine on proteins and UDP-
GlcNac
If you get the mannose-6-phosphate tag, it is important to - ANSWERsend those to
the lysosomes (use outside mannoses to attach phosphate)
2 steps of Mannose-6-Phosphate tag - ANSWER1. phosphotransferase attaches a
phospho-GlcNAc sugar using UDP-GlcNAc as substrate to a mannose on the
glycosylated protein
2. A phosphodiesterase removes the GlcNAc leaving behind a mannose-6-phosphate
labeled protein
Where does mannose-6-phosphate tag occur? - ANSWERin the golgi apparatus
What symptoms do we find in I-Cell disease? - ANSWERskeletal deformities occur
shortly after birth
, Dislocation of hip, retardation in psychomotor development, fatal around 5-8 years
old
Is there a cure for I-Cell? - ANSWERNo
Simple lysosomal storage diseases affect a - ANSWERsingle defective lysosomal
enzyme that causes buildup of specific substance leading to cellular dysfunction
Complex lysosomal storage diseases involve - ANSWERmultiple enzymes that are
defective or unavailable
Common features found in many LSD's - ANSWERlow birth weight, congenital bone
fractures, facial malformations
There are over 50 lysosomal diseases, however, these are very - ANSWERrare
The most common lysosomal storage disease is - ANSWERGaucher's Disease
The major problem in lysosome storage disorders is - ANSWERsubstances aren't
being degraded in the cells, and they are building up until damage occurs
Lysosomal storage disorders are a _____ genetic diseases - ANSWERloss of function
Pathogenic mutations in lysosomal storage diseases occur in ____ or ____ regions of
genome - ANSWERnon-coding, coding
The first step in a lysosomal storage disorder pathogenic cascades -
ANSWERmutation in a gene involved in lysosome homeostasis
Loss of function/reduced protein function (3 ways) - ANSWER1. lead to non-
functional enzyme (it's made but has no activity)
2. enzyme is made but isn't folded properly, then gets degraded
3. enzyme isn't made at all - translated to stop codon
Pathogenic cascade (5 steps) - ANSWERMutation occurs
altered protein leading to loss of function
substrate accumulates leading to increased volume of lysosome
dysfunction of other organelles and cellular processes
triggers macrophages and inflammation
Lysosomal storage disorders can be divided into 2 categories - ANSWER1. general
defects
2. specific defects
Questions & Answers: Updated
Lysosomes are primarily produced from the ____ and become secondary lysosomes
only after ____ with other vesicles (autophagosomes) - ANSWERgolgi apparatus;
fusion
Lysosomes break down large molecules taken into the cell by endocytosis to basic
molecular parts for ____ or ____ into new structures - ANSWERenergy production or
recycling
There are different functions of lysosomes for different materials -
ANSWERproteolytic enzymes, lipolytic enzymes, carbohydrate hydrolyzing enzymes,
nucleic acid hydrolyzing enzymes
Enzyme trafficking to lysosomes (4 steps) - ANSWER1. Lysosomal enzymes are in
inactive form (zymogen) in the ER
2. Post-transitionally modified with Mannose-6-Phosphate
3. Transported from golgi to lysosomes
4. activated in lysosomes by LOW pH
Why are lysosomal enzymes inactivated at first? - ANSWERbecause if not, they
would degrade everything around it (until getting to the right place)
What are lysosomal enzymes activated by ___? - ANSWERlow pH
While in the ER, lysosomal enzymes are also modified by ____. This requires -
ANSWERN-linked glycosylation; Asparagine/Serine/Threonine on proteins and UDP-
GlcNac
If you get the mannose-6-phosphate tag, it is important to - ANSWERsend those to
the lysosomes (use outside mannoses to attach phosphate)
2 steps of Mannose-6-Phosphate tag - ANSWER1. phosphotransferase attaches a
phospho-GlcNAc sugar using UDP-GlcNAc as substrate to a mannose on the
glycosylated protein
2. A phosphodiesterase removes the GlcNAc leaving behind a mannose-6-phosphate
labeled protein
Where does mannose-6-phosphate tag occur? - ANSWERin the golgi apparatus
What symptoms do we find in I-Cell disease? - ANSWERskeletal deformities occur
shortly after birth
, Dislocation of hip, retardation in psychomotor development, fatal around 5-8 years
old
Is there a cure for I-Cell? - ANSWERNo
Simple lysosomal storage diseases affect a - ANSWERsingle defective lysosomal
enzyme that causes buildup of specific substance leading to cellular dysfunction
Complex lysosomal storage diseases involve - ANSWERmultiple enzymes that are
defective or unavailable
Common features found in many LSD's - ANSWERlow birth weight, congenital bone
fractures, facial malformations
There are over 50 lysosomal diseases, however, these are very - ANSWERrare
The most common lysosomal storage disease is - ANSWERGaucher's Disease
The major problem in lysosome storage disorders is - ANSWERsubstances aren't
being degraded in the cells, and they are building up until damage occurs
Lysosomal storage disorders are a _____ genetic diseases - ANSWERloss of function
Pathogenic mutations in lysosomal storage diseases occur in ____ or ____ regions of
genome - ANSWERnon-coding, coding
The first step in a lysosomal storage disorder pathogenic cascades -
ANSWERmutation in a gene involved in lysosome homeostasis
Loss of function/reduced protein function (3 ways) - ANSWER1. lead to non-
functional enzyme (it's made but has no activity)
2. enzyme is made but isn't folded properly, then gets degraded
3. enzyme isn't made at all - translated to stop codon
Pathogenic cascade (5 steps) - ANSWERMutation occurs
altered protein leading to loss of function
substrate accumulates leading to increased volume of lysosome
dysfunction of other organelles and cellular processes
triggers macrophages and inflammation
Lysosomal storage disorders can be divided into 2 categories - ANSWER1. general
defects
2. specific defects
