Final exam select topics-neurotox

Question 1

neuropathy

Answer 1

irreversible death, apoptosis, necrosis (only some myelin left, no axon)

Question 2

axonopathy + where repaired

Answer 2

repaired in PNS not CNS, change in cell body too

Question 3

myelinopathy + where repaired

Answer 3

some repaired in PNS not CNS, slows conduction

Question 4

nissl substance

Answer 4

clusters of ribosomal complex

Question 5

what disease foes trimethyltin chloride make

Answer 5

limbic-cerebellar syndrome (neuropathy)

Question 6

what is a main way that trimethyltin chloride causes limbic-cerebellar syndrome (neuropathy)

Answer 6

stannins

Question 7

what are stannins + where are they

Answer 7

proteins associated with ER and mito

Question 8

where are high levels of stannins

Answer 8

limbic cerebellar areas, hippo amyg

Question 9

what do stannins contain

Answer 9

cytoplasmic metal binding domain

Question 10

how does trimethyltin chloride affect stannins

Answer 10

they bind, causes Ca++ flux then initiates apoptosis

Question 11

what does rayon and CS2 cause (simple)

Answer 11

axonopathy

Question 12

what does CS2 do generally

Answer 12

modified proteins

Question 13

who does CS2 cause irreversible damage to

Answer 13

amino groups (draw it out)

Question 14

who does CS2 cause reversible damage to

Answer 14

sulfhydryl groups (draw it out)

Question 15

what are 2 CS2 markers

Answer 15

valine-lysine and lysine-lysine thiourea

Question 16

where does lysine-lysine thiourea happen

Answer 16

globin

Question 17

where does valine-lysine thiourea happen

Answer 17

spectrin

Question 18

what reaction happens to form acrylamide (what 2 things join)

Answer 18

asparagines and reducing sugars (Maillard reaction)

Question 19

how is acrylamide metabolized + what into

Answer 19

CYP2E1 into glycidamide

Question 20

what is the deal with glycidamide

Answer 20

its a much stronger electrophile than acrylamide (can modify proteins, DNA)

Question 21

what happens to glycidamide

Answer 21

it is converted into glyceramide (non toxic) or detoxed by GSH

Question 22

so what are the 2 compounds in order that acrylamide can become

Answer 22

glycidamide then glyceramide

Question 23

what are the steps to make acrylamide (think maillard, 4 steps)

Answer 23

• asparagine and reducing sugar join
• water loss to make Schiff base
• amadori rearrangement to make amadori compound
• amadori loses CO2 to make acrylamide

Question 24

what is the main acrylamide toxicity (1 main thing)

Answer 24

forms adducts with proteins, esp with SH groups

Question 25

what are 3 possible acrylamide mechanisms

Answer 25

• defective kinesin based anterograde transport
• mitochondrial disfunction (energy deficit)
• direct effect on NT release

Question 26

what kind of toxicity does Domoic acid cause

Answer 26

amnesic shellfish poisoning

Question 27

what causes amnesic shellfish poisoning

Answer 27

domoic acid

Question 28

what is the structure of domoic acid and what is it similar to

Answer 28

tricarboxylic acid, structural analog to kainic acid

Question 29

what is the mechanism of domoic acid

Answer 29

stimulates kainate glutamate receptors to conduct Ca++ into cells (excitatory)

Question 30

does domoic acid cause receptor desensitization

Answer 30

no

Question 31

what part of brain does domoic acid preferentially effect

Answer 31

hippocampus

Question 32

what are the 2 stages of domoic acid poisonings

Answer 32

24 hours is GI

48 is neurolgical

Question 33

what are the 4 compounds that happen after CS2 modified a protein

Answer 33

dithiocarbamate, isothiocyonate then either dithiocarbamate ester or thiourea linkage