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Nutr 3330 > Midterm 2 (Lec 6) > Flashcards

Midterm 2 (Lec 6) Flashcards

1
Q

Fruits and veggies!

A

-Well accepted that consumption decreases rates of cancer and heart disease
- often attributed to antioxidants
- should we go beyond “eat lots of fruits and veggies?

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2
Q

Micronutrient essential antioxidant defense System

A
  • Vitamin E
    -Vitamin C
  • selenium, riboflavin, niacin
  • zinc, copper, manganese
    -Iron
  • beta carotene
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3
Q

Why do we need antioxidants

A
  • All about balance between Pro oxidants and anti oxidants
    -Oppose toxic effects of oxygen
  • 95% of oxygen is used for energy production (good)
  • 1-3.%. Results in production of reactive oxygen species ( can be bad)
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4
Q

Oxidative stress

A

serious imbalance between ROS generation and antioxidant supply
- increased ROS production (many ways)
- decreased antioxidant intake

Cells can sometimes ADAPT: “things remain unbalanced but cells make due ex - insufficiency”

Severe oxidative stress can cause CELL DAMAGE (“accommodation instead of adaptation - something has to change ex- deficiency the accommodation is the symptoms)

Cell damage- cellular mutations, tissue breakdown, immune compromise etc

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5
Q

Free radicals

A

Formed during oxidative metabolism

Contribute to oxidative stress

Molecules with one or more UNPAIRED electrons - VERY unstable and highly reactive

Need to steal an electron from another molecule to stabilize - can set off a chain reaction

Atoms bind together by sharing electrons - two electrons can exist in one bind
- unpaired state (ROS) is unstable and reactive

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6
Q

Types of free radicals

A
  • ROS: reactive oxygen species
  • RNA: reactive nitrogen species
  • R: other reactive radicals

Free radicals are a bi product of normal cellular reactions

They do have useful biological function
- key is to control their quantity

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7
Q

Types of ROS

A

Free radicals
- superoxide radical (O2)
- hydroxy radical (OH)
- fatty acid peroxide radical (ROO)
- nitric oxide (NO)

Unstable molecules
- hydrogen peroxide (H2O2)
- ozone (O3)

Not inclusive list

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8
Q

Reasons for ROS generation

A
  1. Useful production (intended; to deal with sickness)
    - important defence mechanism
    - produced by activated phagocytes
    - mechanism to kill bacteria/fungi and inactivate viruses
  • can be inappropriately activated (inflammatory diseases)
  1. Accidental production
    - instability in the presence of oxygen
    - many molecules spontaneously react with oxygen
    - electron transport chain
    - some electrons escape and react with oxygen : free radicals are formed
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9
Q

Problem with free radicals

A

They’re unstable and need to steal an electron from a non radical to become stable

When they react with non radicals, CHAIN REACTIONS start

Hard to control quantity - products build up and cause cell damage

Best example is lipid peroxidation

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10
Q

Lipid peroxidation

A
  1. Generation of free radical (can be controlled at this point)

RH -> R. + H where R. = free radical

  1. Propagation/chain reaction (what makes free radical uncontrollable)

Free radical is regenerated in the presence of oxygen

R. + O2 -> ROO.
ROO. + RH -> R. + ROOH (fatty acid hydroperoxide- BUILD UP PRODUCT)

and the cycle continues

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11
Q

Fatty acid hydroperoxide (ROOH)

A

Can build up and cause oxidative stress
- disruption of cell membranes, cell damage
Can also combine with IRON:

ROOH + FE2+ -> FE3+ + OH. + RO-

Produced hydroxy radical (most potent free radical)

Iron can also react with H2O2

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12
Q

Hydroxy radical (OH.)

A

Bad bad news - no positive role in the body

Reacts instantaneously with anything - leads to many problems
- initiates free radical chain reaction
- mutates DNA
- possibly cancer initiation
- protein damage; function disrupted

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13
Q

Superoxide (O2.) and hydrogen peroxide (H2O2)

A

Reactive oxygen species’
- superoxide is a free radical
- hydrogen peroxide is an unstable form of oxygen

Much less reactive than OH.
BUT can react with EACHOTHER to form OH. ( worst)
- called the Haber-Weiss reaction; iron is involved

O2.- + H2O2 -> OH. + OH- + O2

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14
Q

Dealing with ROS

A

Need to keep them at a manageable level
Need to prevent oxidative damage - aka need radical scavengers
- answer is ANTIOXIDANTS!

Want antioxidants to react with free radicals before they react with something else (like DNA)

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15
Q

Micronutrient antioxidant defence system

A

Vitamins and minerals from diet plus enzymes that need vitamins and minerals

Allow balance between PROoxidant and ANTIoxidant systems

Goal is to avoid oxidative stress

Beside micronutrients, there are other compounds we can obtain from our diet such as phytochemicals

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16
Q

Micronutrient antioxidant defence system list

A

Vitamin E
Vitamin C
Selenium (glutathione peroxidase) riboflavin niacin (glutathione reductase)
Zinc copper manganese (SOD superoxide dismutase)
Iron (catalase)
Beta carotene

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17
Q

Vitamin E: chain breaking

A

Able to terminate chain reactions

Key structural features
- OH group; reacts with oxygen (ROO.)
- ring structure; makes it a non reactive free radical “and chain makes it fat soluble to stick into cell membrane”

QUENCHES the free radical - acts as an antioxidant

SLIDE 23 AND 24 STRUCTURE

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18
Q

We can deal with the vitamin E free radical

A

The key is Vitamin C - it donates a hydrogen

The vitamin C radical can now recycle back to vitamin C without formation of a free radical ( C can keep going back and forth between stable and radical form)
“Vitamin E also regenerated”

Result is complete quenching of free radical

Vitamin C and E work together :)

19
Q

Vitamin E not ALWAYS present

A

1 vitamin E to 400 fatty acids

Free radical will not always meet vitamin E before attacking cell membrane

We cannot avoid some ROOH from being formed

Still no worries since we have enzymes that can deal with them

20
Q

Glutathione peroxidase and glutathione reductase

A

Deal with build up of ROOH by converting it harmless compounds (when vitamin E is not available)

Both of these enzymes need micro nutrients to work
- glutathione peroxidase needs SELENIUM (takes O from ROOH?)
- glutathione reductase needs RIBOLFLAVIN and NIACIN

21
Q

Another important enzyme: superoxide dismutase

A

Deals with superoxide O2.- radical

Needs
- ZINC and COPPER
- MANGANESE

forms hydrogen peroxide (also unstable)
- then metabolized by CATALASE (needs iron)

22
Q

Iron is ironic

A

BAD
- catalyzes the Haber-Weiss reaction which produces OH.
- also thought to contribute toward the invitation of lipid peroxidation

GOOD
- needed for catalase enzyme to detoxify H2O2

23
Q

Comment on beta carotene

A

Precursor of vitamin A

Unique antioxidant
- depends on partial pressure of oxygen
- low oxygen pressure: acts as antioxidant
- high oxygen pressure: acts as pro oxidant

Quenches singlet oxygen
- singlet oxygen is a free radical itself but a potent generator of free radicals

Can act as anti-oxidant but depends on partial pressure
- relevant to lungs, RBC membrane

24
Q

Free radicals and chronic disease

A

More and more evidence suggesting that certain diseases are associated with free radical damage

Support for a role of antioxidants in
- heart disease
- diabetes
- cancer
- aging

When ROS increases or antioxidant defences decreases, result is oxidative stress

25
Q

Cardiovascular disease

A

Oxidative damage to LDL greatly enhances development of atherosclerosis

Oxidized LDL accelerates several steps in the process of atherosclerosis

Vitamin E inhibits oxidation of LDL
“Oxidized LDL way worse than normal LDL - why antioxidants improve CVD”

26
Q

Cancer

A

Oxidative damage to cells

Harder to study than CVD

intervention trials using supplemental antioxidants not as consistent

27
Q

ATBC and CARET studies

A

ATBC
- the alpha tocopherol beta carotene cancer prevention study

CARET
- carotene and retinol efficacy trial
- beta carotene and retinol efficacy trial

Extreme surprise in antioxidant cancer research

Both studies showed an INCREASE in lung cancer with beta carotene supplementation in male smokers

28
Q

ATBC Study

A

Alpha tocopherol, beta carotene vs placebo

Randomized, double blind, placebo controlled, primary prevention 6 year study (don’t know)

20,000 Finnish male smokers

Beta carotene increased lung cancer 18%
- with or without alpha tocopherol

No effect of alpha tocopherol by itself

Contradictory to accumulating observational evidence that beta carotene and vitamin E are beneficial for cancer

“Know high doses of beta carotene increased cancer”

29
Q

CARET study

A

Beta carotene and retinol efficacy

18,000 men and women: high risk lung CA

high risk lung CA; smoking, asbestos

Beta carotene, vitamin A vs placebo

Terminated after 4 years
- inability to detect benefit
- ATBC trial results were concerning

30
Q

Food vs supplements

A

Canadian and US fruits and vegetables health claims for foods
- fruits and vegetables reduce risk of CANCER
- fruits and vegetables reduce risk of CVD

Many factors including antioxidants involved in this

What are your thoughts on food vs supplements particularly given the ATBC and CARET studies?

31
Q

Vitamin C essentiality

A

Vitamin C or ascorbic acid or ascorbate

Not essential for all species

Humans are one of the few species that cannot synthesize vitamin C

32
Q

Vitamin C Structure

A

Versatile - reversible reaction, can exist in either state

Ascorbic acid/ ascorbate (reduced) <-> dehydroascorbate/ dehydroascorbic acid (oxidized)

33
Q

Vitamin C synthesis

A

Synthesized from glucose

Humans are missing ONE enzyme: gulonolactone oxidase

We actually do have the gene, but it’s mutated (we don’t need it since vitamin C is everywhere in food)

SLIDE 5?

34
Q

Vitamin C metabolic role

A

Calling card of vitamin C:
- hydroxylase reactions:

  • ascorbic acid donates hydrogens and becomes dehydroascorbic acid
  • ascorbic acid is a REDUCING AGENT : keeps compounds in their reduced state (ex - keeps vitamin E reduced)
35
Q

Vitamin C metabolic role summary

A
  • collagen synthesis (scurvy)
  • carnitine synthesis
  • tyrosine metabolism ; catabolism, neurotransmitter synthesis
  • antioxidant
36
Q

Vitamin C: collagen synthesis

A

Linked to scurvy symptoms (tissue breakdown)

Collagen is the largest protein in body and contributes to stability of connective tissue including firmness of skin

Collagen needs to be TOUGH to do this - toughness comes from its hydroxylation (cross linking)
- PROLINE and LYSINE residues must be hydroxylated
- PROLYL/LYSYL HYDROXYLASE
- needs iron as a cofactor “alphaketoglutarate and succinate also in reaction”
- iron must be in reduced state ; ascorbate keeps iron in its reduced state
- this is a post translational modification

37
Q

Vitamin C: carnitine synthesis

A

Carnitine needed to transport fatty acids to mitochondria to be oxidized for energy

Synthesized from lysine and methionine - Two iron dependent hydroxylase enzymes

Ascorbate keeps iron in REDUCED state

38
Q

Vitamin C: tyrosine metabolism

A

Not as well known
Tyrosine -> dopamine -> norepinephrine
- needs dopamine beta hydroxylase and copper (reduced)

39
Q

Vitamin C : antioxidant

A

Direct antioxidant protection
- powerful reducing agent
- neutralizes free radicals and other oxidant species

Indirect antioxidant protection
- ascorbic acid can supply electrons to regenerate the active reduced form of other biological antioxidants
- vitamin E, glutathione, flavonoids

40
Q

Vitamin C: nutrient interactions

A

Minerals have absorption problems

Iron
- enhances absorption of non heme iron
1. Reduced iron to ferrous from ferric form
2. Forms soluble complex with iron
3. Facilitates incorporation into ferritin

Ex: having orange juice with oatmeal for breakfast will do all three of these

Copper
- inhibits copper absorption
- treatment for Wilson’s disease (build up of copper)

41
Q

Vitamin C food sources

A

Citrus fruits

Organ meats

Dramatically reduces during storage
- water soluble therefore can get lost a lot

Highly susceptible to oxidation

42
Q

Vitamin C deficiency

A

Scurvy - major problem in sailors

Symptoms
- FATIGUE
- weakness of collagenous structures and breakdown of tissues (bones, cartilage, teeth)
- impaired wound healing
- hemorrhage in skin, muscles
- bleeding gums

43
Q

Vitamin C: health and disease

A

Common cold
- minimizes inflammatory effects of oxidized products in healthy people
- only effective in prevention?

Cancer
- fruits and vegetables intake protective
- free radical scavenger

CVD
- neutralize oxidized LDL’s

44
Q

Vitamin C toxicity issues

A

Very non toxic - UL IS 22X the RDA

Susceptible populations:

Oxalate kidney stones
- oxalate is a metabolite of vitamin C
- excreted by kidney
- can combine with calcium

Iron metabolism problems
- vitamin C enhances iron absorption
- hemochromatosis

Nutr 3330 (21 decks)

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