antioxidants Flashcards
we eat vitamin C in the form of _______________, which is a ___________, donating both _______s and _______s
ascorbic acid–> reducing agent that donates both e-s and Hs
when ascorbic acid donates an electron, what does it briefly become?
a free radical!
what two steps must occur for ascorbyl radical to be reduced back to ascorbic acid?
must donate another e- to become dehydroascorbic acid and then must be reduced back by glutathione
what does dehydroascorbate reductase need for structural purposes to reduce dehydroascorbic acid back to ascorbic acid?
selenium~
t/f: Vit C recycling is efficient
false! we need to have a constant dietary supply …
what is the deficiency of Vit C + symptoms?
scurvy: bruising, bleeding gums, CT issues, fatigue
what are the top 4 dietary sources of Vit C?
citrus, papaya, bell peps, brussels
what is the RDA for vit C?
m: 90 mg/d
f: 75 mg/d
how is ascorbic acid digested?
trick question! it’s not digested… we eat and absorb straight ascorbic acid
how is ascorbic acid absorbed(2 ways)?
diffusion(small molecule) and transporter
what is the % absorption of Vit C? how is this affected by high ingestion?
75-90%, but this drops with megadoses
how is ascorbic acid transported in the blood? how does it get into cells?
transported freely in the blood(very water soluble/polar)
needs transported to enter cells
t/f: high doses of Vit C are beneficial to increase serum levels in times of illness
false- at about 150 mg/dL, your blood is pretty much saturated and 1K+ mg/d is pretty useless..
at about 100 mg dosage of Vit C, what “storage” cells are saturated with it?
WBC: monocytes, lymphocytes, neutrophils
what is the theory of harm of taking Vit C at very high levels? what are 2 side effects of this?
can it act as a PROoxidant??? causing liver damage OR acting as a cancer killer?
____________ and ____________ are enzymes that insert O/O2 to a molecule
mono and dioxygenases
vit C acts as an e- donor to _______________(# and adjective) enzymes. how many mono and deoxygenases are each of those?
8 mammalian: 2 mono, 6 di
what are the 2 main monooxygenase functions of vit c?
- neurotransmitter synthesis: norepinephrine, serotonin
2. peptide hormone post translational modification
what 3 syntheses by deoxygenases does Vit C participate in?
collagen, carnitine, tyrosine(non essential AA)
what is the main function of carnitine in cells?
transports FA across mitochondrial membrane to undergo B oxidation in there
how many steps of collagen synthesis is Vit C a part of?
only 1!
after collagen gene is translated and transcribed what is formed? what must happen after this for collagen to be formed?
pre collagen peptide chain –> must undergo post translational modification
what process in post translation modification of the alpha collagen chain requires the Vit C dependent enzyme? why is Vit C needed, specifically?
hydroxylation–> Vit C needed to add OH to proline on the pre collagen chain and enzyme needs e- to be donated from Vit C to do this
during the post translation modification of the collagen, what happens to the deoxygenase AND Vit C?
both become oxidized… must be reduced back to donate e- and OH again
t/f: collagen synthesis will still occur with a vit C deficiency
true! but not as much…. deoxygenase will use any e- donor but Vit C is most efficient
after hydroxylation and sometimes ________________, the collagen chain is _____________ed extracellularly
glycosylated… moved extracellularly and cross-linked
collagen is extremely important in what 3 body structures?
skin, teeth, bones
t/f: Vit C is necessary for healthy bones and teeth
true!
how are Vit C and Vit E related?
Vit C can regenerate Vit E to cont its antioxidant activity (from a-tocopheral radical by donating an e-)
what are the 2 main forms of Vit E we consume? what “subdivisions” do each of these have?
tocopherols and tocotrienols… both have alpha, beta, gama, and omega forms…
the alpha form of tocopherols or tocotrienols has R groups off its carbon chain that are ________________s
all methyl groups…
what is the structural difference between tocopherols and tocotrienols?
tocotrienols have 3 DB in carbon chain off the two rings…
which form of Vit E has the most potent antioxidant activity?
alpha tocopherol
how many stereoisomers does alpha tocopherol have?
8!
what is the “problem” with synthetic Vit E supplements?
contains all 8 stereoisomers of alpha tocopherol but 4 of them are automatically excreted by humans and have no functional effect…
__________ Vit E supplements contain all 8 stereoisomers of alpha tocopherol, while ________ does not contain the 4 stereoisomers that are not maintained by humans
“all racemic” v. “natural Vitamin E”
out of all 8 stereoisomers, which form has the most potent antioxidant activity of alpha tocopherol?
RRR
what is the RDA for Vit E in both forms?
15 mg alpha tocopherol from food or 30 mg synthetic b/c 4 stereosisomers cannot be converted
what are the best dietary sources of Vit E?
wheat germ, sunflower seeds, oils(sunflower, safflower), almonds
when eating a good source of Vit E, what is the alpha tocopherol usually bound to? what is this compound called in food(1) and synthesized(2)?
fatty acid… called alpha tocopherol ester in food
in supplements: may be alpha tocopherol acetate or succinate
what is the first step of Vit E digestion?
fatty acid must be cleaved by a pancreatic esterase to free A.T. –> incorporated into micelle
in the enterocyte, A.T. can be incorporated into what 2 things for export?
- *chylomicron
2. one of the HDL particles formed in the enterocyte(but not many of these produced here!)
how does Vit E get into tissues?
cleaved off chylomicrons or lipoproteins by LPL
once a chylomicron containing a.t. reaches the liver, what are 2 things that can happen to the a.t.?
- incorporated into lipoprotein and continues into circulation
- excreted in bile
what is the main function of Vit E?
antioxidant–> neutralizes free radicals by donating an e-
once alpha tocopherol donates an e-, it is called __________. from here, what are the 3 potential pathways for the molecule?
- another antioxidant like Vit C reduces back to alpha tocopherol
- pairs with another alpha tocopherol radical to form dimer that is excreted
- donates another e- to another free radical… but cannot be recycled, so also must be excreted
very rarely, a.t. radical is not paired with another e- somehow and it becomes _______________. what is the implication of this situation?
becomes a pro-oxidant… must eat a wide variety of antioxidants so they can neutralize each other
t/f: “natural” Vit E supplements are as potent as food Vit E
false!
what is the understood units of Vitamin E in the RDA?
RRR alpha tocopherol equivalents(TE)
what are the IU–> aTE conversions for synthetic and “natural” supplemented forms?
1 IU synthetic–> 0.45 RRR aTE
1 IU “natural”–> 0.67 RRR aTE
what food source has the highest proportion of Vit E as alpha tocopherol, esp. RRR stereoisomer?
wheat germ(yum!)
out of the most common oils used in the American diet, which has the most alpha tocopherol?
canola oil(over olive oil, soy, corn)
soy and corn oils have mostly ______ tocopherol, which is not as potent
gamma
why is Vit E unique among the micronutrients?
only has 1 function… act as an antioxidant unlike other micronutrients that usually have several f(x)s
when taking natural v. synthetic Vit E supplements, what is the trend over time in the plasma?
with the same dose of each, the natural form will always result in higher plasma levels of circulating alpha tocopherol(remember: all racemic has 1/2 of the stereoisomers simply excreted from the body!)
carotenoids have great __________ capacity
antioxidant
t/f: some carotenoids can be converted to Vit A in a healthy person
true!
what is the difference between Vit A from plant sources and animal sources?
plant sources: all carotenoids
animal sources: real Vit A(retinol/things that have activity of Vit A)
about _______ carotenoids occur naturally in plants
600
the most easily converted carotenoid to Vit A is what?
beta-carotene
what is the difference between preformed Vit A and provitamin A?
preformed Vit A is the retinols, while pro-Vit A is carotenes that can be converted to Vit A
what are retinoids?
umbrella class of molecules similar to retinol from animals(retinol, retinal, retinoic acid)
what are the 3 versions of functional Vit A? how do these differ from each other?
retinol, retinal, retinoic acid–> differ in the functional groups at the end of their carbon chain
we usually eat functional Vit A forms in the form of____________. what is one example of this?
retinyl ester… EX. retinal palmitate
how are retinyl esters digested?
freed to free retinoids by pancreatic esterases
when we eat carotenes, how are they converted to Vit A? where does this happen?
cleaved in the middle and the L side become Vit A… this occurs in the enterocytes or liver
why are carotenes lipid soluble?
too large/long chain to be water soluble
t/f: some carotenoids cannot be converted to Vit A
true!
what are 3 carotenoids that ONLY have antioxidant(not retinol) activity
lycopene, lutein, zeaxanthin
how does the function of lycopene compare to other antioxidants?
VERY strong antioxidant
what are the best sources of lycopene? (2)
tomatoes, pink grapefruit
what is the at-home implication of carotenoids being lipid soluble?
need to have some fat or oil in cooking to release these antioxidants
how must carotenoids and retinoids be absorbed?
as free molecules(not bound to fatty acids)–> incorporated into micelles once freed and then diffuse into enterocyte
in the enterocyte what happens to carotenoids(3) and retinol(1)?
carotenoids: some converted to retinal–> bound to CRBPII–> retinol–> retinyl palmitate OR retinoic acid OR stay the same
retinol: converted to retinyl palmitate
what is the difference between how retinoic acid leaves the enterocyte v. retinyl palmitate and carotenoids?
retinoic acid secreted into blood and binds to albumin to travel…
retinyl palmitate and carotenoids are incorporated into chylomicrons
what must retinyl be bound to in the enterocyte?
CRBPII
where is Vit A stored in the body? how does this occur? what is the specific cell type in this organ?
in the liver cells–> esters on chylomicron cleaved to retinol–> reesterified in liver’s STELLATE(like stellar storage!!) cells
when the body needs retinol, how does the liver respond?
liver’s STELLATE cells release retinol(cleaves retinyl esters) and binds to RBP(retinol binding protein)–> release complex into blood
in the blood the RBP+retinol complex is called ______________. this additionally binds to ___________, making it less likely to be filtered by the ____________ and be excreted
called transthyretin, which binds to thyroid hormone to prevent excretion(forms TH-TTR)
how does retinol from transthyretin complex (TH-TTR) get into cells?
enzymes on cell surfaces to cleave from the hormone and protein
in tissues, retinol is taken in, but what must happen in the cells?
must be bound to CRBP(cellular retinol binding protein)
what two retinoids can interconvert? which conversion is irreversible?
retinol and retinal can interconvert, but retinal to retinoic acid is not reversible!
name the 3 different categories of functions for the different retinoids
retinal: part of rhodopsin in the retina
retinoic acid: cell differentiation and gene expression
retinol: growth, osteoclast activity
t/f: the body has innate mechanisms to protect against retinol toxicity
true! limits rate of conversion from carotenoids
t/f: if someone eats a vegetarian diet, Vit A toxicity is very rare and bone status is not a concern
true!
what is the Vit A content of most multivitamins?
usually a mix of retinol and carotenes
what is the implication of Vit A for those living in the arctic?
polar bear meat/liver has TONS of retinol, so this specific population is actually at a high risk of toxicity
t/f: retinol from food is not sufficient to reach UL
true`
what are the 3 “compartments” of the retina? what does the lowest level sit next to?
photoreceptor, inter photoreceptor space, pigment epithelium(next to blood)
when RBP-all trans retinol from the blood enters the pigment epithelium, what does it form? what must it be converted to here?
forms CRBP all trans retinol–> converted to 11-cis retinol
when CRBP in the pigment epithelium moves to the inter photoreceptor space, what change occurs?
binds to IRBP(interphotoreceptor retinol binding protein) instead of CRBP
in the photoreceptor, __________ and ___________ combine to form rhodopsin
11-cis retinal and opsin
when light hits rhodopsin, what happens?
opsin splits from the retinal component and the 11 cis retinal becomes ALL-TRANSretinol, then retinal again
**must be transported all the way back through the inter photoreceptor space to the pigment epithelium to be renewed to 11-cis retinal
in order for retinoic acid to have gene expression/cell growth regulation f(x), what two forms must be present? what happens to the two of them before their function occurs?
9-cis and all -trans retinoic acid must both be present… unbound from their CRBPs and become a dimer
in the dimer that moves into the nucleus, all-trans retinoic acid binds to _________ receptors on the DNA, while 9-cis retinoic acid binds to __________ receptors
all-trans binds to RAR receptors
9-cis binds to RXR receptors
what does binding of the retinoic acid dimer to DNA receptors do?
enhances transcription of selected genes with these receptors–> enhances growth and expression of certain proteins
if someone has a Vit A deficiency, what might some symptoms be(2)?
decreased growth, impaired vision
what does RAE stand for?
retinoic activity equivalents
t/f: some carotenes are more easily converted than others
true!
t/f: foods fortified with Vit A usually contain the retinol form
false- usually contain both retinol and carotenes
which converts to retinol more often- dietary or supplemental B-carotene?
supplemental
1 RAE= ? mcg B carotene from supplements v. dietary
1 RAE= 2 mcg supplemental B carotene, but 12 mcg dietary…
which of the carotenes in the family convert most efficiently to retinol?
Beta
1 RAE= ? mcg dietary retinol
1 mcg retinol(1:1 conversion rate)
what is the conversion between IU of Vit A and RAEs for both supplements and dietary retinol
- 33 IU= 1 RAE
* *does not matter if IU is from supplement or food! (already factored into calculation of IU)
what is the conversion of FOOD B carotene IU to RAE?
20 IU food B carotene= 1 RAE
t/f: B carotene is a nutrient
false! but Vit A is, so B carotene can contribute to meeting our needs for Vit A
what is the difference between xenobiotics and free radicals?
free radicals are molecules with unpaired electrons; xenobiotics are chemicals or substances with free radicals in them
what do xenobiotics and free radicals both do in the body?
damage DNA!
generally, free radicals and xenobiotics scavenge electrons and cause damage to what types of molecules? what are examples of this in the body?
typically molecules with double bonds, like FA tails of phospholipids
why are antioxidants necessary to “neutralize” free radicals?
antioxidants easily give up e’s to prevent scavenging “damage” of free radicals taking e’s and causing oxidative damage
which are more dangerous in the body? dead cells or damaged living cells? explain.
damaged living cells–> can still proliferate, creating an army of rogue, damaged cells(ex. cancer)
what are 3 characteristics of tumor cells?
- little contact inhibition
- divide uncontrollably
- pile up in an unorganized way
what are 3 common EXTERNAL sources of free radicals/oxidative stress?
- city pollution/exhaust
- radiation(certain wavelengths like UVB)
- cigarette smoke
internally, processes that generally produce ________ also often produce free radicals. why does this occur?
ATP b/c a lot of the time electron acceptors on the ETC, esp. O becomes a free radical when one electron(unpaired) is accepted
to neutralize free radicals formed, like O2* in the ETC, what two steps must occur?(name enzymes)
superoxide dismutase converts O2 radical to H202, then catalase or glutathione peroxidase converts to H20
what happens if a person does not have enough catalase or glutathione peroxidase in their cells?
superoxide dismutase will convert the O2 radical to H202 but this cannot be neutralized to water, so it actually causes more damage and causes MORE free radicals!
t/f: SOD is considered part of the antioxidant pathway
true… even though it generates another free radical, its one step towards neutralization
what does peroxidation mean?
means the oxidation of a long chain molecule, like a FA
what are two reasons that lipid peroxidation is very concerning?
- self-propogating(continues indef unless antioxidants neutralize free radicals right away)
- auto-catalytic…no enzymes needed for process to occur
what element, if unbound, can cause a previously neutralized FA to become a free radical again?
Fe in its’ 2+ form
the presence of _______, enhances lipid per oxidation by promoting its incorporation into a FA radical
O2
what is the best prevention for ROS(reactive oxidative stress)?
prevention by eating a variety of antioxidants and protein to synthesize antioxidant enzymes: Vit C, Vit E, SOD, glutathione peroxidase, catalase
what does the antioxidant enzyme glutathione peroxidase need for structure? what is the best dietary source of this?
selenium–> eat Brazil nuts!
what is one evolutionary protection v. ROS?
compartmentalization: ETC and many metabolic process occur in/across inner mitochondrial membrane, so it’s less likely for unpaired e’s to “sneak out” to other places and cause damage
if molecules in cells are highly reactive, they are usually _____________
bound to proteins(ex- iron)
what is the most prevalent antioxidant in the cell membrane? in the mitochondria?(2)
Vit E in cell membrane; glutathione peroxidase and SOD in mitochondria
for every location in/outside of the cell, we have more than one antioxidant system. Why is this?
so that we are not dependent on one system to neutralize FRs, otherwise if a deficiency/malfunction in that antioxidant occurs, we are up a creek…
in cancer prevention, we cannot prevent exposure to carcinogens necessarily, but we can prevent activation… what 2 nutrients are known to prevent this?
Vit C and E
what prevents an active carcinogen from reaching DNA targets and actually causing damage? (3 dietary examples)
phenols
isothiocyanates
flavones
if DNA is attacked and mutagenesis occurs, what dietary factors might prevent tumor formation and damaged cell proliferation? (3 examples)
phenols
carotenoids
retinoids
if retinoids are not antioxidants, how do they help prevent tumor growth?
they promote cell differentiation and specified cells are less likely to proliferate if they have mutated than generic stem cells
where does detoxification of most xenobiotics occur? how many stages does this process have?
in the liver! 2 stages
which metabolites of xenobiotics formed in the liver can be excreted?
both primary and secondary metabolites
if a primary metabolite of a xenobiotic is NOT excreted, what might happen to it?
could become a reactive intermediate that causes delayed toxicity, mutations, cancer, etc.
stage II detoxification of xenobiotics in the liver is enhanced by dietary intake of ???
phytochemicals like phenols, flavones, isothiocyanates, etc.
____________ are some of the best sources of isothiocyanates
cruciferous veg
______ and ______ are some of the best dietary sources of phenols
wine and tea/coffee
at low levels of oxidative stress, B carotene works as a __________. however, at high exposure to carcinogens/ROS, what happens with B carotene?
works as antioxidant at low levels… but at high levels, in vitro data actually shows B carotene increase the amt. of unpaired e’s b/c it can block the effect of other, more potent carotenoids
what are the current recommendations re; B-carotene for smokers?
do NOT take a B carotene supplement because it has actually been shown to be harmful and prevent antioxidant activity!
