Lecture 15 - micronutrients part 2 Flashcards
What is a redox reaction?
involves the transfer of electron between two substrates. many biochemical reactions are essentially electron transfers
- large number of micronutrients are involved in redox reactions
What are the primary electron carriers in the body
NADH and FADH2
What is reduction?
electron donor gives its electron to electron acceptor (gained electrons)
What is oxidation?
electron donor loses its electrons to the electron acceptor (lost electrons)
ROS
reactive oxygen species
How are ROS produced?
as a by-product of the ETS when proper electron flow fails
occurs in an O2 rich environment, where oxygen can react with electrons
What are radicals?
elements that have unpaired electrons
What are the steps to reactive oxygen species?
- O2 reacts with one electron in mitochondrial leakage to produce O2’- superoxide anion radical (modest reactivity) or it can ideally react with 4 electrons to produce 2H2O
- superoxide anion radical reacts with another electron using superoxide dismutase (SOD) as donor to produce H2O2 hydrogen peroxide
- from here H2O2 can react with glutathione peroxidase to make 2H2O or react with an electron to make OH’ hydroxyl radical (very reactive)
Is the OH radical bad?
yes, it attacks macromolecules (DNA, lipids) leads to cancer, cell death
What are the molecules that are under the vitamin E umbrella?
8 structurally-related compounds (known as vitamers)
- 4 tocopherols
- 4 tocotrienols
What is a tocopherol?
have saturated s.c. with 16 carbons
What are tocotrienols?
have unsaturated s.c. with 16 carbons
What is the only vitamin E molecule that has significant activity in the body?
alpha tocopherol
Where are vit E vitamers found?
naturally in foods
What are vitamers?
chemical compounds that have similar molecular structure, each showing vitamin activity to some extent
What are some characteristics of tocopherols?
- saturated s.c. (phytyl tail)
- alpha isoform has the most methylated ring
- one of the hydroxyl on the ring is the antioxidant site
- transport mediated uptake in the small intestine
What are the four tocopherols?
alpha
beta
gamma
delta
What are the four tocotrienols?
alpha
beta
gamma
delta
What are some characteristics of tocotrienols?
- unsaturated side chain
- lower levels in food compared to tocopherols
- transport mediated uptake in the small intestine
- tocotrienols have antioxidant activity in the liver only
What are some foods that vitamin E is found in?
nuts, seeds, vegetable oils, avocado
Why is vitamin E mostly obtained in plants?
vit E is stored in adipose tissue in animals and we don’t normally eat the fat
What is a special feature about vit E in foods?
it is sensitive to food preparation and storage
What is the vit E RDA based on?
only alpha tocopherol
How is alpha tocopherol levels determined?
tests that examined the hemolysis of red blood cells in the presence of dilute H2O2
What populations can vit E deficiency occur in?
- pre-mature infants (kept in oxygen rich incubators, which increases oxidative stress) who are then at risk for hemolytic anemia
- people with fat malabsorption disorders or gallbladder removed, which can reduce absorption of dietary fats
- people with genetic defects in lipoproteins or TTP, which prevents transports of alpha-tocopherol around the body
How is alpha-tocopherol absorbed?
RRR-alpha-tocopherol binds to tocopherol transfer protein (TTP) in the small intestine and gets packaged into VLDL (chylomicron) and goes to extrahepatic tissues
- chylomicron remnants are taken up by the liver
What makes TTP?
the liver makes TTP, which is needed to get alpha-tocopherol into VLDL
Where is vit E stored?
no specific storage organ for vit E, but most of it goes into lipid droplets in adipose tissue
What are the steps to the metabolism of vit E?
- vit E becomes vit E radical (R’ PUFA peroxyradical -> RH PUFA hydroperoxide) vit E donates its electron
- vit E radical can either become vit E dimer to go into bile (2/3) or become quinone to go into urinary excretion (1/3)
- regeneration of active vit E can occur through vit C in vitro turning Vit C into dehydroascorbate
Why is selenium content in food determined by selenium levels in soil?
plants incorporate selenium from the soil into methionine and cysteine amino acids instead of sulfur
How and where is selenium absorbed?
selenoAA are absorbed in the small intestine by amino acid transporters and travel freely in the blood
What type of selenium does the body use?
selenocysteine
how many selenocysteine proteins are there in the body?
30
What happens if there is a selenium deficiency?
china and africa (low se in soil)
keshan disease (cardiomyopathy from cell damage by free radicals)
Is selenium toxicity rare?
yes, but if it occurs, its called selenosis - chronic consumption of lots of brazil nuts which are rich in selenium can lead to hair and nail loss
What type of AA is selenocysteine?
non-standard AA (proteinogenic)
What are the two selenoproteins involved in oxidant defense?
glutathione peroxidase
fatty acid peroxidase
GSH
glutathione
What is GSH?
used as a substrate (reducing agent) for glutathione peroxidase and fatty acid peroxidase (selenoproteins) in oxidant defense
What is the structure of glutathione?
glutamate and cysteine (thiol group) amino acids are linked through a gamma carbon - this gamma peptide bond is resistant to cellular proteases
- glutathione itself doesn’t have selenium in its structure
How does glutathione function steps?
Redox rxn 1:
2GSH —> GSSG
GSH - reduced, donates 2 e-
GSSG - oxidized (selenoprotein)
- at the same time converts H2O2 to 2H2O using the enzyme GSH peroxidase
- at the same time PUFA hydroperoxide is converted to PUFA alcohol using the enzyme FA peroxidase
PENTOSE PHOSPHATE pathway
Redox rxn 2: (at the same time)
NADP+ —> NADPH + H+
NADP+ - oxidized
NADPH + H+ - reduced
enzyme: glutathione reductase (riboflavin/vitB12)
GSSG
gluthione disulfide (selenoprotein)
What is the ratio of GSH to GSSG in a healthy cell?
> 90% GSH and <10% GSSG - highly cellular levels of GSSG indicative of high oxidative stress
What is vit C also known as?
ascorbic acid, at physiological pH, known as ascorbate
What is a structural characteristic of vit C?
exists in both D- and L- stereoisomers, only L-isomer is biologically active in humans
What are the mammals that cannot synthesize vit C from glucose?
humans primates fruit bats guinea pigs and some birds, lack the enzyme glyconolactone oxidase
What is the uronic acid pathway?
glucose (or galactose) -> gulonolactone -> ascorbic acid
(gulonolactone oxidase)
What is the primary source of vitamin c?
fruits anf vegetables
What is vitamin C sensitive to?
heat, light, oxidation and alkaline solutions
Does vit C require digestion prior to absorption?
no
How and where is vit C uptake occurring?
via sodium-dependent vit C (SVCT) 1 and 2 transporters in the small intestine
What percentage of dietary vit C is absorbed?
70-90%
How is vit C found in circulation?
in its free form, not bound to a protein
What kind of vit C do foods contain?
ascorbic acid, but can have small amounts of the oxidized form (dehydroascorbic acid)
Where are vit C concentrations high?
white blood cells as well as many tissues
What is vit C involved in?
collagen synthesis
tyrosine synthesis
neurotransmitter synthesis
biological processes
What type of agent does vit C primarily act as?
reducing agent
What are the two biologically active forms of vit C?
ascorbic acid (reduced)
dehydroascorbic acid (oxidized)
What are the steps to post-translational modification of procollagen?
procollagen becomes proline OH through the enzyme prolyl hydroxylase and post translational modification
proline OH then is exported to extracellular space
What does proline OH do?
pro-Oh is what allows the collagen molecules to stick together
WHat percentage of AA in procollagen are prolines?
30% of the AA in procollagen are prolines, 1/3 of which are hydroxylated
What is the role for vit C in the posttranslational modification of procollagen?
prolyl hydroxylase-Fe2+ becomes prolyl hydroxylase Fe3+ using proline to proline OH, it can be reversed but requires ascorbic acid to become dehydroascorbic acid
(electron donated from vit C to form proline OH)
What are the RDA trends for pregnant women for vit C?
increased in pregnant and lactating women to support mother and fetus
What are the signs of a vit C deficiency?
- scurvy: plasma vit C levels are very low, if you consume 10mg of vit C per day, scurvy will develop within 1 mo
- increased risk of hemorrhages (skin, follicles, gums)
- increased hair loss, loose teeth
- swollen joints, poor wound healing
