Selenium Flashcards
active form
amino acid selenocysteine (SEC)
where Se replaces S; this amino acid is in selenoenzymes
such as glutathione peroxidase (GPx)
Se can also be found in proteins as selenomethionine but this is not “active”
Selenium Absorption
Organic (SEC, selenomethionine) - can be taken up whole but can’t use as direct sources of SEC – must break down to obtain Se and make new SEC
Inorganic forms (selenite, selenate) can be used as sources of Se
All forms efficiently absorbed, so not a key regulatory point
Other metals (e.g. mercury) as well as phytate can prevent absorption
organic form absorption
selenomethionine or selenocysteine
in stomach -> amino acid transoporter
selenoamino acids -> portal blood
inorganic form absorption
all small intestine:
diffuse through membrane or uptake via ATPase
convert to selenate (SeO4) to portal blood and VLDL or LDL
chelation absorption
small intestine
heavy metals and phytates bound to Se
excreted or uptake through diffusion to portal blood
Se Metabolism
To make a protein containing SEC (selenocysteine), an enzyme converts seryl-tRNA to SEC-tRNA DURING translation.
unlike GLA and OHPro which are post-translational changes to aa already in a protein
This allows addition of the amino acid SEC to the growing protein chain
Several proteins (selenoenzymes) require SEC for their function:
Glutathione peroxidase (GPx)
5’-Deiodinase
How is SEC incorporated into a protein?
Seryl-t-RNASEC is converted to SEC-t-RNASEC by adding Se to serine
Then SEC is added to the peptide chain (This is a translational change)
Thus “SEC is not merely CYS with a Se instead of S” – it is a unique amino acid added during protein synthesis
Glutathione Peroxidase GPx
Seven known isoforms of GPx (GPx1-7) - contain selenocysteine
Peroxides (H2O2, LOOH, ROOH) converted to H2O LOH, ROH
e.g., 2H2O2 + 2GSH —–> 2H2O + GS-SG
H2O2 or LOOH/ROOH -> 2 GSH -> 2 GSSG
2 H2O or H2O + LOH/ROH
5’- deiodinase (5’-DI)
Important for iodine metabolism as T4 (thyroxin)
predominant transport form to convert to “active” form (T3)
5’-DI Removes 5’ iodine from T4
T4 ➜T3
If low in 5’DI activity, then low conversion of T4 to T3, thus less activity of the hormone
Se deficiency? activity of selenoenzymes?
Tissue hierarchy
In some tissues, activity (e.g. liver, plasma), but in other tissues, very little if any change (e.g. brain)
Hierarchy among selenoenzymes
Some are decreased much more (e.g. GPX1) than others (e.g. GPX4)
Food Sources Se
soil determines amount in vegetables and meat
meat levels > alts and grains
fish
brazil nuts 800mcg/30gm grown in high conc soil
RDA Se
= 55mcg men and women
how was EAR set
based on amount needed to maximize synthesis of
GPx.
studies in China and New Zealand showing low intakes
(due to low soil) low GPX.
EAR set using amount of Se in diet + amount of
supplement in these low Se countries that allowed for
sufficient GPX activity
is Se deficiency as issue for Canadians
no, plasma levels goof, intake exceeds RDA, diets from different areas of the country
Se deficiency in livestock
Generally Se deficiency alone not too bad, but if
deficient or marginal in other nutrients (e.g. vitamin E)
then situation is worsened.
Human deficiency in China Se
Keshan disease which is Se deficiency causing
fibrosis of heart (Se prevents but does not treat; thought to be
viral problem exacerbated by Se deficiency)
New studies indicate effect on viruses that may explain why many
new flu strains originate in low Se areas of China
= Nonpathogenic virus converted to pathogenic virus in a
Se-deficient host.
This effect of virulent viruses is thought to cause symptoms in
Keshan disease
Kashin-Beck disease
degeneration of joints
Se deficiency implicated
Recent finding: if in area of high arsenic (As) such as
Bangladesh, low Se allows As toxicity to manifest, but high
Se is protective
Saskatchewan lentils high in Se sold in Bangladesh to
alleviate As toxicity
UL Se
400mcg all sources
Hair/nail brittleness (specific signs- selenosis) – seen in an area in China where soil/water Se very high naturally.
These signs, not very “toxic”, but not reversible
Other signs/symptoms (e.g. excess supplements) – nausea/vomiting, fatigue, diarrhea, muscle cramps
At very high levels (gram amounts) Se is lethal – organ damage
how was UL set
based on seeing hair/nail brittleness (“selenosis”) as well as other signs of Se toxicity
5 patients in China seen over a period of years with selenosis at intakes > 900 ug
Eastern Wyoming and Western South Dakota = high Se area with no selenosis < 700 ug
NOAEL set at 800 μg (in-between 900 μg and 700 μg); UF = 2 because irreversible UL = 800/2 = 400 μg
