Klinisk Biokemi i Norden Nr 3, vol. 31, 2019 - page 14

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Klinisk Biokemi i Norden · 3 2019
form in food, as well as other seleno-analogues of
thio compounds and inorganic selenium are rapidly
absorbed (2,10). Subsequently, dietary selenium is
converted to selenides before incorporation into
specific selenoproteins. In humans, selenomethio-
nine is also incorporated unspecifically by replacing
methionine in proteins. Surplus of free selenides are
excreted as selenosugars, and at high doses methyla-
ted for urinary excretion.
Following absorption and metabolism in the liver
selenium is distributed to other organs mainly protein
bound to selenoproteins P, which is taken up in other
organs via a receptor-mediated mechanism. Another
selenoprotein in plasma is GPx3, which is synthesized
in the kidneys. About one third of plasma selenium
is found
unspecifically
incorporated as selenomethio-
nine at the expense of methionine (2,10).
Selenoproteins - synthesis and functions
The human selenoproteome consists of 25 seleno-
proteins, and in addition, there are isoforms of these
owing to alternative posttranslational modifications
(1;2;11). SeCys is
specifically
incorporated into seleno-
proteins by the selenocysteine insertion machinery,
which is different from the other amino acids. Before
incorporation, inorganic and organic selenium from
the diet have to be converted to hydrogen selenide
and selenophosphate (Figure 2). The subsequent bio-
synthesis of selenocysteine (SeCys) takes place on its
own specific tRNA, initially charged with serine that
reacts with selenophosphate to form SeCys-tRNA.
The insertion is in all selenoprotein-mRNAs guided
by the UGA codon. The SeCys insertion sequence
(SECIS) element at the end of the mRNA coding sequ-
ence of selenoproteins, recruits specific proteins and
SeCys-tRNA. Compared to cysteine, a pool of free
SeCys is neither desirable nor required because of its
toxicity due to its reactivity towards, i.a. molecular
oxygen with production of reactive oxygen species
(ROS) (12).
Most of the selenoproteins contain one SeCys
residue. Important exceptions are selenoprotein P
(SELENOP), which contains 10 SeCys residues. The
selenol group plays an important role in the bioche-
1...,4,5,6,7,8,9,10,11,12,13 15,16,17,18,19,20,21,22,23,24,...44
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