CMB Exam 2 - Drugs/Toxins

Question 1

thermogenin (UCP1)

Answer 1

Physiological uncoupler of oxidative phosphorylation. Many hibernating animals express this and it keeps them warm.

Question 2

hydroxyurea

Answer 2

Antineoplastic drug that inhibits ribonucleotide reductase.

Question 3

methotrexate

Answer 3

Inhibit dihydrofolate reductase, reducing dTMP/inhibiting pyrimidine synthesis.

Question 4

CO in the ETC

Answer 4

Binds the cytochrome oxidase in Complex IV of ETC, preventing e- transfer to O2 (just like cyanide and azide).

Question 5

2,4-dinitrophenol (DNP)

Answer 5

Powerful uncoupler of oxidative phosphorylation.

Question 6

azaserine

Answer 6

Glutamine antagonist (inhibits purine and pyrimidine synthesis) like acivin.

Question 7

Explain this image of rotenone inhibition of ETC:

Answer 7

Mitochondria can make ATP with the proper enzymes and a C substrate (malate), O2, Pi and ADP. Once ADP is added, O2 is used for ATP synthesis. Adding rotenone inhibits Complex 1, stopping O2 usage. Add succinate and O2 usage resumes because succinate DH uses FADH2 which bypasses Complex I. ADP is depleted and ETC stops again.

Question 8

allopurinol

Answer 8

Inhibits xanthine oxidase (its metabolite alloxanthine plugs the enzyme)

Question 9

sodium benzoate

Answer 9

Used to treat hyperammonemia in liver cirrhosis nad UC enzyme deficiencies. Combines with glycine to form hippuric acid and is cleared by the kidneys.

Question 10

amytal

Answer 10

Barbiturate, blocks e- flow in Complex I of ETC (similar to rotenone)

Question 11

oligomycin

Answer 11

“Plugs” the H+ pump of ATP synthase, preventing charge equalization and inhibiting e- flow in ETC.

Question 12

acivicin

Answer 12

Glutamine antagonist (inhibits purine and pyrimidine synthesis) like azaserine

Question 13

sodium phenylacetate

Answer 13

Used to treat hyperammonemia in liver cirrhosis nad UC enzyme deficiencies. Conjugates with glutamine and is cleared by the kidneys.

Question 14

azide

Answer 14

Binds the cytochrome oxidase in Complex IV of ETC, preventing e- transfer to O2 (just like CO and cyanide).

Question 15

bortezomib

Answer 15

Proteasome inhibitor, approved for myeloma treatment.

Question 16

5-fluorouracil

Answer 16

Inhibits thymidylate synthase, reducing dTMP/inhibiting pyrimidine synthesis. Can also be incorporated into DNA and stop synthesis.

Question 17

antimycin A

Answer 17

Blocks flow of e-s from cytochrome b to c1 (ie clocks flow from Complex III of ETC).

Question 18

trimethoprim

Answer 18

Inhibit dihydrofolate reductase, reducing dTMP/inhibiting pyrimidine synthesis.

Question 19

cyanide

Answer 19

Binds the cytochrome oxidase in Complex IV of ETC, preventing e- transfer to O2 (just like CO and azide).

Question 20

Explain this image of Antimycin A inhibition of ETC:

Answer 20

Mitochondria can make ATP with the proper enzymes and a C substrate (malate), O2, Pi and ADP. Once ADP is added, O2 is used for ATP synthesis. Adding Antimycin A inhibits Complex III, stopping ETC. Succinate does not bypass Complex III, but ascorbate (vitamin C) can donate e-s to cytochrome C in vitro, so ATP production resumes until ADP is depleted.

Question 21

rotenone

Answer 21

Insecticide, blocks flow of e-s through Complex I of ETC (just like amytal).

Question 22

Explain this image of cyanide/azide/CO inhibition of ETC:

Answer 22

Mitochondria can make ATP with the proper enzymes and a C substrate (malate), O2, Pi and ADP. Once ADP is added, O2 is used for ATP synthesis. Adding cyanide/CO/azide blocks ATP synthase, so nothing is able to get ATP synthesis to resume.

Question 23

pyrimethamine

Answer 23

Inhibit dihydrofolate reductase, reducing dTMP/inhibiting pyrimidine synthesis.