L16: Reactive Oxygen Special and Detoxification Pathways

Question 1

radical

Answer 1

• single unpaired electron

Question 2

biradical

Answer 2

• two single unpaired electrons

Question 3

free radical

Answer 3

• independent ability to interact with other molecules

Question 4

superoxide radical

Answer 4

• produced in ETC

- O2*

Question 5

hydrogen peroxide

Answer 5

• interacts with iron and copper to produce hydroxyl radicals

Question 6

hydroxyl radicals

Answer 6

• OH*

- most reactive species

Question 7

how super oxide is formed in ETC

Answer 7

• coenzyme Q interacts with and transfers electrons to O2

Question 8

CCl4

Answer 8

• common cleaning solvent that is converted to CCl3* radical
• by cytochrome P450
• initiates damage to ER - cell death and liver damage

Question 9

ionizing radiation

Answer 9

• splits H2O into hydroxyl and hydrogen radicals

Question 10

monoamine oxidase

Answer 10

• inactivates dopamine in neurons

- generates H2O2 at mitochondrial membranes causing neuronal damage

Question 11

lipid peroxidation

Answer 11

• can spread through membrane
• lipid degradation
• membrane integrity disrupted

Question 12

protein damage

Answer 12

• certain protein residues are oxidized and protein fragments, degrades or cross links
• pro, his, arg, cys, met

Question 13

DNA damage

Answer 13

• base alterations

- strand breaks

Question 14

nitric oxide

Answer 14

• neurotransmitter and hormone

- single electron

Question 15

nitric oxide synthesis

Answer 15

• from arginine via citruline

Question 16

nitric oxide single electron

Answer 16

• can combine with O2 or superoxide to form reactive oxygen species with both nitrogen and oxygen

Question 17

macrophages and NO

Answer 17

• use NO at high concentrations to kill pathogens

Question 18

NO in inflammation

Answer 18

• combines with superoxide to form peroxynitrite that can damage proteins, lipids, and DNA by oxidation and nitration

Question 19

respiratory burst

Answer 19

• phagocytic immune cells respond to pathogens by rapid consumption of O2

Question 20

respiratory burst reaction

Answer 20

• O2 -> O2- via NAPH oxidase
• O2- -> H2O2
• H2O2 form HOCl by myeloperoxidase
  
  • effective against bacteria\
• H2O2 forms hydroxyl radicals

Question 21

neutrophils

Answer 21

• for NO when activated by inducible nitric oxide synthase
• and also activate NADPH oxidase
  
  • forms superoxide

Question 22

superoxide dismutase

Answer 22

• converts superoxide to H2O2

Question 23

catalase

Answer 23

• converts H2O2 to H2O and O2

Question 24

glutathione peroxidas

Answer 24

• reduces H2O2 to water and lipid peroxides to alcohols

- requires NADPH to replenish via glutamine reductase

Question 25

antioxidants

Answer 25

• donate a hydrogen to neutralize radicals

Question 26

vitamin E

Answer 26

• fat soluble
• protect membranes
• terminates lipid peroxidation radical to form more stable lipid peroxide

Question 27

vitamin C

Answer 27

• regenerates vitamin E

Question 28

uric acid

Answer 28

• traps free radicals in plasma and production reaction products that are excreted

Question 29

xenobiotics

Answer 29

• potentially toxic compounds and drugs
• body metabolizes
• liver is primary site of detox

Question 30

phase I reactions

Answer 30

• reduction, oxidation, hydroxylation, hydrolysis
• form hydroxyls
  
  • make less toxic

Question 31

phase II reactions

Answer 31

• add negatively charged groups
  
  • conjugation, sulfating, methylation, glucouronidation
• allows it to be excreted

Question 32

cytochrome P450-dependent monooxygenases

Answer 32

• phase I enzymes

Question 33

NADPH-cytochrome P450 reductase + cytochrome P450

Answer 33

• NADPH donates electrons to reductase then transfers them to cytochrome P450
• P450 binds O2 and chemical substrates
• oxidizes substrates

Question 34

CYP34A

Answer 34

• metabolizes greatest number of drugs

- competition amongst drugs for this enzyme could cause reduced drug potency

Question 35

vinyl chloride

Answer 35

• used in plastics

- carcinogenic

Question 36

vinyl chloride phase I

Answer 36

• converted to chloroethylene oxide by CYPE21
  
  • an epoxide
• binds to proteins to cause cell damage

Question 37

vinyl chloride phase II

Answer 37

• converted to chloroacetaldehyde
• conjugated to glutathione via glutathione-s-transferase
• excreted

Question 38

what to avoid with vinyl chloride detox

Answer 38

• avoid buildup of chloroethylene oxide

Question 39

normal pathway of acetaminophen

Answer 39

• normally excreted safety after glucoronylation or sulfation

Question 40

high doses of acetaminophen

Answer 40

• CYP2E1 produces NADPQI (toxic intermediate)

Question 41

NADPQI

Answer 41

• conjugated with glutathione and excreted safely

Question 42

CYP2EI and alcohol

Answer 42

• induced by alcohol (MEOS system)

- alcohol consumption causes more acetaminophen to be directed to NAPQI and greater toxicity for a given dose