Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

VI. Selenium
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and other lipid peroxides (ROOH) also function as substrates.
The product is an acyl moiety wherein the [ OOH]
group is converted to an [ OH] group. Mice genetically
designed to lack GPx1 are in many respects phenotypically
normal, indicating that the enzyme is not critical for life.
However, other variants (e.g., GPx4) are lethal and die during
early embryonic development ( Burk and Hill, 2005 ;
Stadtman, 2000) .
2 . Iodothyronine Deiodinase
In addition, another family of selenoproteins is the 1,5 -
iodothyronine deiodinase (EC 3.8.1.4) (5 -ID). The
enzyme, 5 -ID, catalyzes the 5 -monodeiodination of thyroxin,
the major secretory product of the thyroid gland,
to its active form 3,3 ,5-triiodothyronine ( Koenig, 2005 ).
Deiodination by 5 -ID occurs in peripheral tissues (e.g.,
liver, kidney, and muscle). In Se deficiency, activity of type
1,5 -iodothyronine deiodinase is decreased along with the
concentration of thyroxin.
3 . Other Proteins
A number of proteins have been identified that are presumably
important to Se transport and delivery to organelles
and tissues (e.g., the plasma protein, selenoprotein P)
( Burk and Hill, 2005 ). Selenocysteine is also found in thioredoxin
reductases, formate dehydrogenases, and glycine
reductases. In addition, Waschulewski and Sunde (1988)
demonstrated that in dietary methionine deficiency, selenomethionine
could be incorporated into proteins in place of
methionine. This important observation indicates that several
identified “ selenoproteins ” cannot be dependent on Se
per se for their structure or function, but rather might arise
from the incorporation of the methionine.
4 . Se and Viruses
Recent work has also demonstrated that deficiencies in
either Se or vitamin E can in certain cases increase viral
pathogenicity by changing relatively benign viruses into
virulent ones, an example wherein host nutritional status
should be considered a driving force for the emergence
of new viral strains or newly pathogenic strains of known
viruses ( Beck, 2007 ).
C. Selenium Metabolism, Absorption, and
Transport
Absorption of Se occurs mainly in the duodenum with little
evidence of uptake by the rumen, abomasums, stomach,
jejunum, or ileum. In monogastric animals, absorption of
soluble forms of Se (selenite, selenocysteine, selenomethionine)
is very high ( 80%) and does not appear to be
homeostatically controlled ( Finley, 2006 ). Absorption of Se
in ruminants is lower than in nonruminants (about 40%),
presumably because of the reduction of selenite to insoluble
forms of Se in the rumen. Elemental Se and Se sulfide
are not absorbed to any appreciable degree ( Ammerman
et al. , 1995 ; Spears, 2000, 2003) . After absorption, there
appears to be a rapid distribution of water-soluble Se compounds
to most organs.
Transport in plasma to various organs seems to involve
selenoprotein P ( Burk and Hill, 2005 ). Selenoprotein P is
an abundant extracellular glycoprotein that is rich in selenocysteine.
Four isoforms of selenoprotein P have been
identified. They share the same N terminus and amino
acid sequence. One isoform is full length and the three
others terminate at the positions of the second, third, and
seventh selenocysteine residues normally present in the
full-length protein. In rats, it has been estimated that 25%
of whole-body Se passes through this protein each day.
Selenoprotein P knockout mice have low Se concentrations
in the brain, testis, and fetus. Measurement of selenoprotein
P in human plasma has shown that it is depressed by
Se deficiency and by cirrhosis. Of potential importance, Se
supplementation optimizes glutathione peroxidase activity
before Se in selenoprotein P is optimized, indicating that
plasma selenoprotein P can be a better index for assessing
Se nutritional status.
Although the intracellular processing of Se remains
poorly understood, it is known that before the incorporation
of inorganic Se (selenite or selenate) into amino acids,
it must be reduced to selenide (-SeH), a process requiring
glutathione. Se is excreted primarily through the urine and
appears to be dependent on a renal threshold. Fecal and
respiratory losses are important routes, depending on species.
Ruminants have relatively higher fecal Se losses than
nonruminants, because of reduction or the complexing of
Se in the rumen making it unavailable for absorption.
Concentrations in the diet of sulfur (inorganic and as
sulfur-containing amino acids), proteins containing high
amounts of sulfur amino acids, and phosphates can affect Se
absorption/excretion. The order of uptake in Cacao cells is
SeO 3 or to selenocysteine to selenomethionine to
SeO 4 . Both amino acid-related and anion transporters are
involved in Se transport. Many of the details, however, have
yet to be resolved. For example, the transport of selenomethionine
is inhibited by its sulfur analogue, methionine,
whereas inhibition of the transport of selenocysteine by
cysteine is not observed. The transport of SeO 4 is inhibited
by thiosulfate, but not sulfate ( Burk and Hill, 2005 ; Finley,
2006 ; Spears, 2003 ). A number of intestinal inflammatory
diseases and short-bowel syndrome can lead to Se deficiency
( Burk and Hill, 2005 ; Finley, 2006 ; Spears, 2003 ).
In other cells, common Se compounds (selenate, selenite,
selenomethionine, and selenocysteine), are taken
up rapidly through anion-exchange transporter systems.
Uptake through anion-exchange carriers is followed by