UNIT 10: MICRONUTRIENTS II; Vit E, Selenium, Vit C Flashcards
Oxidants act as ____ agents and Anti-oxidants act as ____ agents.
Oxidizing agents.
Reducing agents.
NAD is derived from ___ while FAD is derived from ___.
NAD - vitB niacin
FAD - vitB riboflavin
How are ROS formed?
O2 instead of ideally accepting 4e- to form H2O,
O2 accepts 1 or 2 e- to form –> ROS
What is a radical?
an unpaired e- in an orbital
Rank the order of reactivity of ROS and formation.
O2 (chain of donating e-)
- mitochondrial leakage –>
- superoxide anion radical (modest reactive)
- -> via superoxide dismutase (SOD)
- hydrogen peroxide (modest reactive)
- -> via reduced iron or copper (e- donors)
- hydroxyl radial (most reactive)
What are some biological roles of ROS?
- T3/T4 synthesis (H2O2 needed to attach iodide)
- arachidonic acid –> eicosanoids
- immune function (macrophage generates to kill)
What are the 2 types of oxidant defense systems?
- non-enzymatic
- enzymatic defense
Vitamin E and Vitamin C work as a part of which oxidant defense system?
non-enzymatic defense
Zinc, copper, manganese, selenium work as a part of which oxidant defense system?
enzymatic defense
What is the overall role of vitE in oxidant defense?
protect against lipid damage by hydroxyl radical
What is the overall role of of vitC in oxidant defense?
regenerate E to improve GSH:GSSG ratio
What is the overall role of copper, zinc, manganese in oxidant defense?
help superoxide dismutase (SOD) convert superoxide anione to hydrogen peroxide
What is the overall role of selenium in oxidant defense?
required for glutathione peroxidase
- converts hydrogen peroxide H2O2 –> water
What is vitamin E?
fat soluble vitamin
- mostly plants, less in animal tissues
How does vitamin E act as an antioxidant?
- it donates e- to reduce damaging oxidant molecules
- it is the chain breaking antioxidant
What is the first line of oxidant defense?
glutathione (GSH) peroxidase
- selenium required
- converts H2O2 –> H2O
What is the second line of oxidant defense?
vitamin E
- chain breaking anti-oxidant
What is the only active/natural form of vitamin E? Dietary recommendations (RDA) for this form only.
RRR-a-tocopherol
R = natural configuration of methyl
What is the difference in structure of tocopherol and tocotrienol?
tocopherol - saturated
tocotrienol - unsaturated (-ene)
What is TTP?
Tocopherol Transfer Protein
- incorporates tocopherol as a required form of vitE into VLDL to send to extrahepatic tissues
- does not recognize tocotrienols - therefore not part of RDA
What is the chain breaking antioxidant defense?
- role of vitamin E
- breaks the chain of lipid peroxidation initiated by hydroxyl radical
How is the superoxide anion radical formed?
O2 –> superoxide anion radical
- leakage of e- from ETC
How is H2O2 formed?
superoxide anion radical –> H2O2
- superoxide dismutase
How is hydroxyl radical fomed?
H2O2 –> OH . (hydroxyl radical)
- reduced by iron or copper
What are the reactions involved in lipid peroxidation?
- hydroxyl radical (OH . ) attacks PUFA
= PUFA free radical (short lived) - PUFA free radical + O2 = PUFA peroxyradical
- vitamin E breaks PUFA peroxyradical before it attacks another PUFA
- -> forms PUFA hydroperoxide
What happens to PUFA hydroperoxide?
product of vitE breaking down PUFA peroxyradical
- degrade to short aldehyde
or
- degraded by fatty acid peroxidase enzyme to reduce to fatty acid alcohols
What is the third line of antioxidant defense?
Fatty acid peroxidase enzyme
- uses selenium and glutathione (GSH) as electron donor
- converts PUFA hydroperoxide –> fatty acid alcohols
How is the vitE radical metabolized?
- vitE radical that formed from PUFA peroxy –> PUFA hydroperoxide
- vitE radical is regenerated by vitamin C –> active vitE
- vitE dimerizes to be excreted in the feces in bile
- vit E is incoroporated to quinone and excreted in urine
What causes vitE deficiency?
not diet!
- mutation in TPP (TPP moves vitE to be incorporated to VLDL to extrahepatic tissues)
- gall bladder removed/impaired pancreatic damage
- premature infants who are exposed to too much O2 (ROS)
What are effects of vitE toxicity?
- one of the least toxic vitamins but damage can cause muscle weakness, fatigue, GI distress
- increases in hemorrhagic CVD
What is selenium?
a micromineral
- soil selenium is incorporated into cysteine and methionine via plant foods
What are 3 forms of selenium in the diet?
- selenocysteine
- selenomethionine
- selenite (inorganic)
What is the role of selenium in oxidant defense?
Selenoprotein enzymes:
- GSH peroxidase
- Fatty acid peroxidase
Glutathione GSH substrate is a _____ agent. It ____ __ electrons.
- Reducing agent
- donates one e-
- therefore, 2 GSH are required for 2 e- transfers
Both GSH peroxidase (1) and FA peroxidase (3rd line of defense) require selenium as the form of..
active selenocysteine
GSH peroxidase uses 2GSH molecules, donates 2 e- to convert ____ to ____.
FA peroxidase uses 2GSH molecules, donates 2e- to convert ____ to ____.
GSH peroxidase:
H2O2 —> H2O
FA peroxidase
FAOOH = PUFA hydroperoxide –> FAOH = PUFA alcohol
GSH is converted to ____ during (GSH/FA) peroxidase activity
GSSG
- ratio of GSSG increases as peroxide activity increases
How is GSH regenerated?
2 e- donated from NADPH to 2 GSSG –> 2GSH
How is NADPH regenerated?
HMPS
- hexose monophosphate shunt
(it also makes ribose sugars for DNA/RNA)
What is the engine that drives oxidant defense?
HMPS
- chronic upregulation of HMPS genes
What is a healthy ratio of GSH:GSSG?
90% GSH
10% GSSG
too much GSSG = indicator of oxidative stress
What is Keshan’s disease?
deficiency in selenium
- Keshan county in China - low selenium diet
What is vitamin C?
water soluble vitamin
= ascorbic acid
Vitamin C is synthesized in the small intestine of humans. True/False
False.
Humans cannot synthesize vitamin C.
- due to lack of gulonolactone oxidase
- converts glucose/galactose –> ascorbic acid
What is the role of vitamin C?
oxidant defense
- electron donor to vitamin E radical –> reduced vitamin
Vitamin C deficiency changes ____ GSH:GSSG.
increase in GSSG and decrease in GSH
Vitamin C is also required for ____ reactions, and _____ modfication
- hydroxylation reaction (indirectly)
- post-translational modification of pro-collagen
Vitamin C is essential for the formation of _____
collagen
Explain how procallagen is post-translationally modified.
- procollagen goes under post-translational modification
- hydroxyl groups are added to proline via prolyl hydroxlase
Prolines account for 30% of amino acids in procollagen. Prolines are modified –>
hydroxyproline via prolyl hydroxylase
How is vitamin C involved in procollagen modfications?
- Prolyl hydroxylas has reduced iron in centre
- when proline is hydroxylated to hydroxproline, iron centre is oxidized to Fe3+
- VitaminC/ascorbic acid, donates an e- to reduce Fe3+ to Fe2+
- prolyl hydroxylase Fe2+ is now active
How does vitC treat colds?
- reduce oxidized products from WBC viral infections and decrease inflammation
What are symptoms of vitC deficiency?
- impaired collagen synthesis (teeth, hair loss, wound healing, bleeding gums)
- low absorption of iron in small intestine
What are indicators of vitamin C toxicty?
- diarrhea (osmotic effects)
- kidney stones (urine excreation of oxalate and urate)
- rebound scurvy infants with vitC-supplementing mothers
