Lysosomal Storage Diseases (LSDs)

Question 1

Tay-Sachs Disease

Answer 1

First LSD
-Deficiency of HEXA (beta-hexosaminidase A, alpha-subunit)
-Gene location: chromosome 15q24.1
-Results in the accumulation of GM2 ganglioside
-Death of neurons in the brain and spinal cord

Question 2

Autophagy

Answer 2

-Major cellular pathway to degrade proteins and organelles in the lysosome
-Digested components are recycled and reused
-Essential role in starvation, cellular differentiation, cell death and cell aging

Question 3

Anti-cancer agents

Answer 3

Proteasome inhibitors

Question 4

Lipofucsin

Answer 4

-Brownish-gold pigment
-Generally seen in non-dividing cells
-Accumulates over years: “Wear and tear” pigment
-Conglomerate of lipids, metals, organic molecules

Question 5

Hemosiderrin

Answer 5

-Brown pigment
-Iron-storage complex found in the cytoplasm
-Likely formed by indigestible residues of hemoglobin: easily demonstrated in the spleen

Question 6

Melanin

Answer 6

-Brown pigment

Question 7

Glycogen

Answer 7

-Non-membrane bound, TEM dense bodies
-Storage form of glucose: catabolism releases glucose for energy

Question 8

Lipid

Answer 8

-Non-membrane bound, TEM dense
-Fat droplets: spherical droplets of triglyceride
-Liquid at body temperature
-Energy store and source of short carbon chains for membrane synthesis
-Lipid storage disease (lipidoses)
-Lipid droplets accumulate in abnormal amounts or locations

Question 9

Colchicine

Answer 9

Anticancer compound that prevents polymerization and binds to unpolymerized tubulin molecules
-If given to dividing cells, mitotic spindle breaks down
-Programmed cell death
-Related compounds : vinca alkaloids, vinblastine, vincristine

Question 10

Taxol

Answer 10

Anticancer drug
-Stabilizes and prevents microtubule disassembly
-Preferentially binds tubulin within assembled microtubles
-Arrests dividing cells in mitosis: unable to achieve metaphase spindle conformation
-Programmed cell death

Question 11

Cilia arrangement

Answer 11

9+2 microtubule arrangement
-Pair of Dynein arms, with motor protein, binds adjacent microtubule
-Anchored to cell via the basal body

Question 12

Primary cilia arrangement

Answer 12

9+0 arrangement
-Microtubule based, antennae-like structure

Question 13

Photoreceptors

Answer 13

-Outer segment of rods derived from primary cilia

Question 14

Chemoreceptors

Answer 14

Odor detection by receptors on primary cilia of olfactory neurons

Question 15

Mechanoreceptors

Answer 15

Primary cilia of epithelial cells monitors the flow of fluid through the kidney tubules
-Defects underlie a variety of disorders

Question 16

Protrusion

Answer 16

Actin polymerization at plus (+) end protrudes lamellipodium

Question 17

Attachment

Answer 17

-Focal adhesions anchor the actin cytoskeleton to the extracellular matrix via integrin proteins

Question 18

Contraction

Answer 18

Bulk of the trailing cell & cytoplasm is drawn forward

Question 19

Filopodia

Answer 19

Finger-like projections
-Core of long, bundled actin filaments

Question 20

Lamellipodia

Answer 20

Sheet-like structures

Question 21

Pseudopodia

Answer 21

-3 Dimensional projections

Question 22

Extravasation steps:

Answer 22

1. Rolling
2. Activation
3. Adhesion
4. Transendothelial migration: process of diapedesis (extension of a pseudopod between endothelial cells, pass through the basement membrane into the tissue)

Question 23

Chemotaxis

Answer 23

-Movement within the tissue along a chemotactic gradient towards the source of inflammation