Nutrients, Oxidation and Antioxidants Flashcards
Is vitamin E water or lipid soluble?
Lipid soluble
Is vitamin C water or lipid soluble?
Water soluble
What is oxidative stress?
O2 will steal an electron from a reduced metal, flavin etc and become superoxide) O2-
Superoxide and its products are known as;
Reactive Oxygen Species or ROS
The gas hormone nitric oxide (NO) is known as a;
Reactive Nitrogen Species (RNS)
How are ROS and RNS formed?
By accident in the electron transport chain
On purpose by immune cells
What can have its structure modified by oxidative or nitrosative stress?
Proteins, lipids, carbohydrates, individual nucleotide bases
Is it good or bad that a hydroxyl group can react with anything around it?
Bad
What can aldehydes do that are considered bad?
Create cross links between proteins
How is iron important?
Key role in many enzymes (cytochromes)
Catalysis and electron transfer, oxygen transport
How is iron toxic?
It is insoluble in presence of oxygen
Catalyzes the Haber-Weiss-Fenton Reactions
Produces a free radical hydroxyl
How does iron help defend against the toxins it makes?
With Superoxide dismutase to aid in conversion of superoxide to more stable form
Where and how is iron stored?
In ferritin and hemosiderin mostly in the liver
What molecule moves iron from various organs and cells into tissues and bones?
Transferrin
How much iron should a person have in a day to maintain stores?
At least 8 mg
How is the transferrin receptor complex internalized?
By receptor medicated endocytosis
How is iron release?
By acidification
How is non-heme iron uptake inhibited?
By phytate and polyphenols in common food (plant sources) like;
- black tea
- cocoa
- chamomile
Polyphenols numerous rings chelate the iron increasing its elimination
How is iron uptake stimulated?
Vitamin C
Organic acids
Heme
What is a hereditary excess in iron called?
Hemochromatosis
What is a dietary overload of iron called and how can someone get it?
Hemosiderosis
Alcohol (red wines) and over using supplements (children)
What drugs does iron decrease the absorption of?
Thyroxine, tetracyclin, ciprofaloxacin
occurs because numerous rings on the molecules act as chelators and this more effectively eliminates the drug and iron along with it
What is anemia?
Abnormally low blood hemoglobin
What enzymes can protect you from reactive oxygen species?
Superoxidase dismutases
Catalases
Peroxidases
What chemicals can protect you from ROS?
Bilirubin, glutathione, catalase, vitamin E, B-carotene and ascorbate (vit C)
What is glutathione?
A small tripeptide reversibly oxidized/reduced and can be regenerated by NADPH and glutathione reductase
Superoxide Dismutase
catalyzes superoxide to hydrogen peroxide
What is the danger in an ischemic/reperfusion injury?
the initial return of oxygen creates a burst of ROS species
Reactive Nitrogen species -RNS
NO
Peroxynitrite is ONOO- which is O2- + NO
Although H2O2 is not a free radical but …
it can generate free radicals by encountering a transition metal
Lipid degradation generates
Peroxyl radicals
HOCl
produced by neutrophils during respiratory burst
Peroxynitrite
RNOS
strong oxidizing agent that is not a free radical
can generate NO2 which is a radical
what AA is important because it can be reversibly oxidized and reduced?
Methionine
this requires a reduced thiol such as glutathione
why are aldehydes so detrimental?
they crosslink proteins preventing them from functioning and making the breakdown and elimination difficult
What is Vit E’s role in lipid oxidation ?
it prevents propagation of damage by acting as a sponge
Influx of intracellular calcium causes?
cellular death through activation of numerous intracellular pathways
what complicates the monitoring of oxidative damage in the vascular system?
oxidative damage not necessarily reflected by biomarkers and cannot be used as therapeutic targets
damage build ups in the subendothelial space
Haber Weiss Fenton reaction
(1) Fe+2 + O2 -> Fe+3 + O2-
(2) 2 O2- + 2H+ –> H2O2 + O2
(3) Fe+2 + H2O2 –> OH* + OH- + Fe+3
What transition metal in non reactive in biosystems?
Zinc
In regards to reduction potential, the more negative it is ….
the more likely it will GIVE UP electrons
What aids Iron absorption?
Vit C by acting as an electron donor converting Fe+3 to Fe+2 which is more soluble
In general, what effects metal solubility?
very insoluble at pH 7
but most are very soluble in acid
Freidreich ataxia
hereditary ataxia
defective frataxin - Fe cant be exported from Mitochondria and iron builds up in the nervous system
What metal is required for Iron absorption?
Cu
What can Fe deficiency lead to ?
lead poisoning because DMT/Divalent metal transporter expression is increased and it nonspecifically uptakes other metals as well
What molecules act as buffers to maintain electrical potentials in cells?
NAD(P), glutathione and Ascorbate
all these uptake electrons at different ranges to cover a wide range of redox potentials to maintain the electrical balance in cells
similar to how pH is maintained in the blood
How was it determined that Vitamin E was a requirement in the human body?
Patients with fat malabsoprtion syndromes were shown to have low levels of vitamin E
What sequesters Fe and Cu ions which prevents ROS?
Ceroplasmin (Cu), albumin (metals) and transferrin
What is Vitamin E actually?
A collection of molecules which function like alpha-tocopherol (alpha, beta, gamma, delta)
What is the main function of vit E?
Antioxidant
Stops propagation of free-radical damage in membranes
May prevent fatty acid damage in membranes
Tocopheryl esters (a form of vit E) are broken up by;
Pancreatic esterases (which also break up fatty acids)
What is essential for vit E absorption?
Bile acids
Deficiency occurs in fat malabsorption
which makes sense since Vit E is fat soluble
True or False
Like other fat soluble vitamins, E accumulates in toxic levels.
False
What uptakes vit E?
Chylomicrons
How is vit E oxidized and excreted?
Omega-oxidation by cytochrome P450
Removed in urine or bile
What large organ is also important for vit E excretion?
Skin - sebaceous glands
If there is a deficiency in vit E what are some diagnosis that can develop?
Retintis pigmentosa, neurological symptoms
There is only one type of organism that can make vit E, what is it?
Plants
Best sources are veggie oils
If you are deficient in alpha-tocopherol symptoms of ____ are mimicked.
Freidreich’s ataxia
What can regenerate reduced vit E?
Vitamin C
What is vit C’s main function?
Collegen biosynthesis
converts Proline to hydroxyproline
converts Lysine to hydroxylysine for crosslinking
L-ascorbic acid is derived from ____.
D-glucuronate
structure similar to glucose, can be uptaken by GLUT4
How many electrons can vit C donate? What does it use to regenerate?
2
NAD(P)H or glutathione
What is a deficiency in vit C called?
Scurvy
What are some symptoms of scurvy?
Connective tissue weakness, vascular damage, hemorrhagia, bleeding gums, poor wound and bone healing
What happens if there is excess vit C?
Hypoglycemia (blocks glucose uptake), kidney stones, indigestion, dissolves tooth enamel
No direct evidence that megadose helps colds or flu
What organ needs the most vit C?
pituitary gland
maybe cause its highly sensitive oxidative damage?
Do vitamins C and E aid in primary prevention of total cancer incidence or mortality?
No
In women with cardiovascular event who have high risk CVD, does ascorbic acid, vit E or beta carotene protect against it?
No
Do vit C and E help prevent prostate cancer?
No
Does vitamin C decrease the risk of diabetes?
Yes
Does multivitamin supplementation prevent cancer or CVD?
Perhaps, very limited evidence
what chemicals absorb electrons?
bilirubin, glutathione, ascorbate (vit c)
Glutathione is a small tripeptide composed of …
glutamate, cysteine and glycine
what contributes to Glutathione’s reversibly oxidation/reduction ability?
it is a sulfhydryl, the sulfur atoms can easily lose electrons or be partially ionized
it can also be nitrosylated
What state is the glutathione pool maintained in ?
Reduced state (SH)
S-S) is the oxidized state (from 4 to 2 electrons
What are the defenses in the blood/plasma against reactive oxygen species?
Vitamin C
Bilirubin
uric acid
why can’t an anemic (low heme) pt be given IV heme?
Free Heme in the body is actually toxic
Its is normally bound to Haptoglobin or Hemopexin in the blood. The molecules clean up heme from lysed RBCs
LDLs contain a significant amount of ?
Vitamin E which helps to protect them oxidation
what improves bioavailability of Vit E?
the fat content of food
2 times more available when taken with milk vs. OJ
Can vitamin E be stored?
yes in Adipose tissue
What else is Vit C involved in?
synthesis of adrenal hormones
drug metabolism
folate metabolism
stimulates iron uptake
what patients should consider taking nutrient supplements?
older adults
pregnant women
pt who are food insecure
alcohol dependent
strict vegetarians and vegans (for these ppl when genetics may affect nutrition)
those on drug regimens that alter metabolism/excretion
A common measure of oxidative stress in plasma?
Malondialdehyde
