Translation

Question 1

Zellweger Syndrome

Answer 1

Transport into peroxisomes is mediated by proteins on the surface of peroxisomal membrane.
Mutations in these proteins impair transport.
Zellweger syndrome:
One form of the disease due to mutations in peroxin Pex2 leads to:
Empty peroxisomes (severe peroxisomal deficiency)
Patients have brain, liver, kidney abnormality.
Death soon after birth.

Question 2

I-Cell Disease

Answer 2

I cell disease is a lysosomal storage disease
Characterized by phase-dense intracytoplasmic inclusions in the fibroblasts of patients: inclusion cells, or I-cells
Mental deterioration, skeletal deformities, very short life span
Molecular basis:
Deficiency of mannose-6-P attaching enzyme (N-acetylglucosamine-1-phosphate transferase).
–> deficiency in hydrolases in lysosome
can still accept cargo that needs to be degraded –>accumulate substrate inside the lysosome because cannot degregate

Consequences: No transport of lysosomal enzymes to lysosomes. Lysosomal enzymes accumulate in circulation.

Question 3

autosomal dominant hypercholesterolemia

Answer 3

Autosomal dominant hypercholesterolemia is caused by mutations in LDL (low density lipoprotein) receptor.
Patients have elevated levels of cholesterol (LDL cholesterol)
High risk of coronary artery disease
LDL receptor is involved in removal of LDL from circulation (via endocytosis)

mutation in LDL receptor (on extracellular side)–> cannot bind to LDL to bring into cell to be taken up into lysosomes –> more LDL in circulation

Question 4

Hereditary Emphysema

Answer 4

Impairment of Protein Secretion

alpha1- antitrypsin (secreted from hepatocytes and macrophages).
Inhibits trypsin and blood protease elastase.

alpha1- antitrypsin deficiency in hereditary emphysema is due to:
A point mutation in alpha 1- antitrypsin ==>
Mutation causes improper folding and prevents secretion of alpha1- antitrypsin.
alpha1- antitrypsin accumulates in ER

In the absence of alpha1- antitrypsin
Elastase degrades the fine tissue in lungs