Lysomsomal Diseases 3-24 Sarge

Question 1

From what cellular structures are lysosomes made?

Answer 1

Rough ER (adds sugars to proteins)–> Cis Golgi (also adds sugars to proteins)–> Trans Golgi –> Transport vesicles –> Lysosomes (lipid bilayer )

Question 2

Defect of Tay-Sachs

Answer 2

Hexosaminidase A(HexA), usually created by four nucleotide insertion causing frameshift (infantile form of the disease), build up of GGm2

Question 3

Ganglioside Gm2

Answer 3

lipid broken down (catabolized) by hexosaminidase A and Gm2 acitivator (pulls ganglioside Gm2 out of the membrane), it is a ceromide with different sugars attached

Question 4

describe ganglioside Gm2 processing

Answer 4

glucose is first sugar covalently attached, HexA clips off GalNAc, then the other two sugars leaving only ceramide

Question 5

Cell functions disrupted by GGm2 build up

Answer 5

swollen lysosomes that are not able to perform other catabolic functions- “chokes the cell”, GGm2 conc. rise inside and outside of cell, GGm2 in plasma membrane increases

Question 6

Feature in eyes of Tay-sachs children and cause

Answer 6

“cherry red spot” on the retina, where area around the red is made more opaque by the extra lipids, the red areas are cells that do not accumulate as much GGm2

Question 7

heterozygous incidence of Tay-Sachs mutation in Ashkenazi Jews, French Canadians, Cajuns

Answer 7

1/27 (Dor Yashoran society matchmaking example), 1/30, 1/30 respectively

Question 8

Defect of Gaucher’s disease

Answer 8

beta-glucocerebrosidase- usually cleaves the glucose from ceramide in the lipid glucocerebroside

Question 9

Cell type affected most by gaucher’s disease

Answer 9

marcophages, called “gaucher cells” when affected, enlarged

Question 10

2 symptoms of gaucher’s disease

Answer 10

Most common lysosomal storage disease hepatosplenomegaly, thrombocytopenia, anemia, progressive neurologic symptoms, skeletal and pulmonary involvement

Question 11

Treatment for Gaucher’s disease

Answer 11

enzyme replacement Cerezyme(by injection of beta-glucocerebrosidase), substrate reduction (oral reduces glucocerebroside synthesis)

Question 12

Defect of Niemann-Pick disease

Answer 12

acid sphyngomyelinase (gene SMPD1), breaks sphyng. down to ceramide and PHOSPHOCHOLINE. Causes a build up of sphyg. in the form of droplets and lack of strucutral lipid ceramide in a “neimann-pick cell” Type A is MOST severe case

Question 13

heterozygous incidence of Tay-Sachs mutation in Ashkenazi Jews, French Canadians, Cajuns

Answer 13

1/27 (Dor Yashoran society matchmaking example), 1/30, 1/30 respectively

Question 14

Defect of Gaucher’s disease

Answer 14

beta-glucocerebrosidase- usually cleaves the glucose from ceramide in the lipid glucocerebroside

Question 15

Cell type affected most by gaucher’s disease

Answer 15

marcophages, called “gaucher cells” when affected, enlarged

Question 16

2 symptoms of gaucher’s disease

Answer 16

Most common lysosomal storage disease hepatosplenomegaly, thrombocytopenia, anemia, progressive neurologic symptoms, skeletal and pulmonary involvement

Question 17

Treatment for Gaucher’s disease

Answer 17

enzyme replacement (by injection), substrate reduction (oral)

Question 18

Defect of Niemann-Pick disease

Answer 18

acid sphyngomyelinase, breaks sphyng. down to ceramide and phosphocholine. Causes a build up of sphyg. in the form of droplets in a “neimann-pick cell”