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Food Toxicology -TOX30306 > Week 3 - oxidants + antioxidants > Flashcards

Week 3 - oxidants + antioxidants Flashcards

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1
Q

what are the three types of oxidants seen ?

A
  1. Reactive oxygen species ROS (O2˚, ˚OH, H2O2, 1O2)
  2. Reactive species derives from ROS (LOO˚ or L˚)
  3. Reactive nitrogen species (NO˚, HONOO)
  4. Air polluting gassses (O3, NO2, cigarette)
  5. Compounds with radical metabolites (paraquat)
  6. Transition metals (lead, manganese, cobalt, copper, iron)
  7. Metal contaning proteins (chlorophyl, hemoglobin, myoglobin, cytochrome C)
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2
Q

What are the various source of ROS ?

A
  1. decoupling one-electron transport chains
  2. Enzymatic reactions
  3. Redox cycling
  4. Inflammation neutrophils / macrophages
  5. From other ROS like Haber-weiss reaction
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3
Q

T or F : macrophage and neutrophils can be a source of ROS

A

true

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4
Q

What is the final electron acceptor of the oxidative phosphorylation?

A

final electron acceptor is O2 and this generates H+ gradient which generate ATP

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5
Q

Decoupling one electron transport chain (oxidative phosphorylation) can lead to the production of ____

A

superoxide anion radical (O2˚). 1 radical is produced for every 650 molecules

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6
Q

The uncoupling by cytochrom P450 enzyme containing iron as a cofactor can lead to the formation of ___ and ___

A

H2O2 (peroxide) and O2˚- (superoxide anion radical)

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7
Q

What is the enzymatic reaction that can create H2O2 as a byproduct

A

xanthine oxidase. Produced H2O2 when forming uric acid

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8
Q

How does paraquat generates ROS ?

A

Paraquat is reduced by an enzyme giving an extra electron and then paraquat gives that extra electron to oxygen to form superoxide anion (O2˚)

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9
Q

Tissue damage: Can cause inflammation by neutrophils that release____

A

O2˚-

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10
Q

How are ROS produced in the inflammation site

A

produced from NADPH and O2 by neutrophil-NADPH oxidase. The electrons are taken from NADPH and goes to the oxygen to form superoxide anion (O2˚-)

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11
Q

What is the Haber-Weiss reaction ?

A

Formation of reactive hydroxyl radicals OHfrom less reactive O2-and H2O2

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12
Q

Haver weiss reaction is the rxn in which there is the formation of reactive ___ from less reactive __ and ___

A

hydroxy radicals (OH˚- ) from less reactive O2˚-and H2O2

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13
Q

In the Haber Weiss rxn, you need ___ to be able to form the very reactive hydroxy radical

A

iron

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14
Q

What are the type of dammage that can be initiated by oxidative / ROS

A

1- oxidation of proteins / enzymes leading to a loss of functions
2- oxidation of DNA (mutation / cancer)
3- Oxidation of unsaturated FA (lipid peroxidation / toxic side products)

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15
Q

T or F : in the case of aerobic life, the production of ROS is unavoidable

A

true, since it is part of the natural processes of respiration

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16
Q

What are the reactions that take place during lipid peroxidation

A
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17
Q

What is the effect of lipid oxidation in membranes ?

A

the lipid oxidation will disturb the membrane structure because of the disturbance of the double bounds / orientation of the lipids and this will lead to cell death.

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18
Q

What are the defense mechanism of the body againt ROS

A
  1. Antioxidants molecules that will scavandge free radicals : example vit C, vit E, carotenoids, GSH, coenzye Q10, polyphenols
  2. Antioxidant enzymes that will reduce the levels of ROS (example superoxide dismutase, catalase, glutathione peroxidase)
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19
Q

What are the enzymes that will reduce the levels of ROS in the body

A 
superoxide dismutase (SOD)
catalase
glutathione peroxidase (Se-GPx)
20
Q

T or F : there is an antioxidant enzyme in the body that reduces the levels of hydroxy radicals (OH˚)

A

false

21
Q

QUESTION EXAM : What are the various reactions catalised by antioxidant enzymes (catalase, gutathione peroxidase, superoxide dismutase)

A
22
Q

T or F : antioxidant enzymes need to work together for the detoxification of ROS

A

true, looking at the picture, you can see here that to fully detoxify the superoxide anion radicals, it is not enough to only have the SOD because it will form hydrogen peroxide and so these can have a heiber weiss reaction (O2 and H2O2) to create OH radicals which are very reactive.

23
Q

Why are selenium supplements sometime sold as antioxidant supplements ?

A

Because it is the co-factor of the enzyme glutathione peroxidase which catalise the reaction :

H2O2 + 2 GSH –> 2H2O + GSSG

24
Q

What is the list of AOX (naturals) seen in class

A
  • carotenoids
  • vitamin E = tocopherols
  • vitamin C = ascorbic acid
  • polyphenols like flavonoids
  • peptides (glutathione, lactoferrin)
  • conjugated linoleic acid (CLA)
  • coenzyme Q (ubiquinone)
25
Q

What is the list of synthetic AOX seen in class ?

A

BHT and BHA

26
Q

How does AOX work ?

A

Remember : there is a major caracteristic of the AO because the mode of action is that it donates the e- to scavandge the radicals. It can donate either 1 electron or 2 electron (proton). It will form a AOX radical but this radical needs to be stable or else it is not an AOX.

27
Q

How does vitamin C and vitamin E works to scavandge free radicals ?

A
  1. giving an electron from an OH group
  2. Stabilisation by tautomerism : so the radical form of vitamin C or E is not reactive
28
Q

T or F : antioxidants can also become prooxidants

A

true, example of carotenoids, vitamin E, vitamin C, BHT/BHA, polyphenols (quercetin/hypericin)

29
Q

What was the finding of the study of beta-carotene in smokers

A

4-5 times increase in plasma levels of beta-carotene (by supplements) cna lead to increased risk of lung cancer in smokers.

30
Q

T or F : carotenoids rich diets can reduce the risk of lung cancer, cardiovscular disease, cataract. Carotenoids deficient diets can increase the risk of lung cancer.

A

ture

31
Q

What are the mechanisms of the procarcinogenic action of beta-carotene?

A
  1. Induction on the P450 enzymes (more toxic metabolites for smoke chemicals)
  2. Induction of P450 that degrade retinal / b-carotene and the degradation products disturb retinal signaling (activation of oncogenes and suppression of tumor suppressor genes)
32
Q

T or F : an ADI was establish for the use of b-carotene supplements in smokers

A

false, no adi could be established since this is not a safety concern provided that the intake from the additive is not more than the amount likely to be ingested from a regular consumptions of foods (so it will be below 15 mg/day (level that do not reveal an increaed cancer risk)

33
Q

T or F : the intake of vitamin E supplementation in smokers also increased the icidence of lung cancer

A

false, it had no effect

34
Q

What was the results of the vitamin E intake meta analysis ?

A

that intakes at high dose levels is harmfull since it increases the mortality risk

35
Q

T or F: High dose vitE supplementation may increaseall-cause mortality

A

true, found in a meta study on vitamin E and this is true for all cause mortality, so supplementation of vitamin E is not needed.

36
Q

T or F: you do not need vitamin C supplementation

A

true because the dose for good health is 40 mg/day and the normal diet dose gives 100 mg / day

37
Q

What is the problem with the vitamin C and iron suuplements given to increase the bioavailability of iron (since it is in the reduced form)

A

the problem is that the Fe2+ can form :

1- superoxide anion (O2˚)

2-OH˚

3- split LOOH forming LO˚

38
Q

What is the pro-oxidation mechanism of quercetin?

A

formation of supeoxide anion and peroxide. The radical created is then transformed into a quinone which is also reactive.

39
Q

t or f : Quercetin: at very high levels: dose-related decrease in AOM related tumor incidence

A

true

40
Q

what is the mechanism of protection of quercetin ?

A

toxic quinone production that induces protective enzymes. So this shows that a little toxicity can sometime be beneficial.

41
Q

What is the downside of using too much st john’s wort (hypericin)

A
  1. adverse effect drug interactions since it induces the CYP450 (BCP and HIV might be less effective)
  2. photosensibilisation / skin lesion since hypericin is unstable and forms radicals / polyphenols and causes problems in the skin
42
Q

which of the AOX have ADI and which do not have ADI

A
43
Q

What are the beneficial roles of ROS and RNS

A

Neutrophils play a role in innate immune system and produce O2-as part of the defense mechanism.

44
Q

What were the results seen with exercise and AOX supplement intake

A

Exercicse increases the levels of SOD and GPx (reduces the ROS) but intake of AOX prevents the beneficial effect of excercise.
it also prevents the induction of molecular mediator of insulin sensitivity

45
Q
A

Food Toxicology -TOX30306 (9 decks)

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