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

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Chapter | 22 Trace Minerals
reduction by glutathione-requiring steps. Important is that
some oxyanions, such as chromate, can inhibit uptake,
which GPx activity and activation and subsequently, glutathione
depletion. As a final point, respiratory losses (as
methyl selenides) increase as Se intake increases, although
respiratory losses of Se are thought to be minimal under
most circumstances ( Burk and Hill, 2005 ; Finley, 2006 ;
Spears, 2003 ).
1 . Novel Aspects of Se Metabolism
Unlike other amino acids, selenocysteine, which is at the
active site of selenoproteins, is not coded using a conventional
codon. Selenocysteine is encoded in a special way
by a UGA codon that normally acts as a stop codon in
transcription (Stadman, 2002) . The UGA codon is made
to encode selenocysteine by the presence of a SECIS element
(the selenocysteine insertion sequence) in selenoprotein
mRNAs. SECIS elements are stem-loop structures
located in the 3 untranslated regions (UTRs) of eukaryotic
selenoprotein mRNAs that are required for directing
cotranslational selenocysteine incorporation at UGA
codons. Previous characterization studies of the mammalian
SECIS elements indicate these elements are highly conserved
in type 1 deiodinase, GPx, and selenoprotein P
( Burk and Hill, 2005 ).
When cells are grown in the absence of Se, translation
of selenoproteins terminates at the UGA codon, resulting
in a truncated, nonfunctional enzyme. The primary and
secondary structures of selenocysteine tRNA also differ
from those of standard tRNAs, most notably, a long variable
region arm, and substitutions at several well-conserved
base positions (Stadman, 2002) .
The selenocysteine tRNAs are initially charged with
serine by seryl-tRNA ligase, but the resulting Ser-tRNA
is not used for translation because it is not recognized by
other translation factors. Rather, the tRNA-bound seryl
residue is converted to a selenocysteyl-residue by the
pyridoxal phosphate-containing enzyme selenocysteine
synthase. The resulting selenocysteyl-containing tRNA
(Sec-tRNA) is recognized and is next specifically bound
to a translational elongation factor that delivers Sec-tRNA
in a targeted manner to the ribosomes translating mRNAs
for selenoproteins. Other details regarding this process
are beyond the scope of this chapter. Suffice to say that Se
metabolism from translation to cellular delivery is novel in
keeping with its sulfur-like electronegative chemical properties
(Stadman, 2002) .
D . Disorders of Selenium Metabolism
1 . Se Defi ciency
The major biochemical lesions that are associated
with Se deficiency are low GPx and 5 -ID activities ( Beck,
2007 ; Koenig, 2005 ). Excess cellular free-radical damage
can be the initial lesion underlying the widespread pathologies.
Consistent with this idea are the observations that
simultaneous deficiencies of other antioxidants (i.e., hypovitaminosis
E and A) amplify the signs of Se deficiency
when they occur.
Signs of Se deficiency in humans and domestic animals
have been well described and include degenerative changes
of several tissues, reproductive and growth defects,
immune defects, increased susceptibility to cardiovascular
disease, and some cancers. The interplay of many nutrients
will greatly influence expression of disease ( Fig. 22-3 ).
Se status, either toxicity or deficiency, will directly
affect the free-radical scavenging system, which can be
expressed as clinical disease. For example, nutritional muscular
dystrophy is a Se-responsive disorder that principally
affects young farm animals (sheep, cattle, pigs, horses,
poultry). This myopathy is typically associated with excessive
peroxidation of lipids, particularly the mitochondrial
lipids, resulting in degeneration, necrosis, and subsequent
fibrosis of myofibers. Often this is associated with cardiac
involvement and, depending on the species, hepatic necrosis
( Arthur, 1998 ).
Poultry and swine can be affected by exudative diathesis
and edematous conditions that respond to supplemental
Se. In poultry, the condition typically affects the pectoral
muscles but can also involve the gizzard and other skeletal
muscles. In mammalian species, the muscles of locomotion
are usually more severely affected (dorsal spinous
and appendicular muscles). Nutritional pancreatic atrophy
is a specific Se-responsive condition in chicks. Deficiency
of Se alone will induce the condition, and it is apparently
related to a severe alteration of the endoplasmic reticulum
and not mitochondria as previously thought. This condition
results in a loss of functional pancreatic acinar cells.
In swine and cattle, mastitis has been shown to be Se
responsive ( Arthur, 1998 ; Koenig et al. , 1997 ; Smith et al. ,
1987 ; Spears, 2000 ). Testicular degeneration and impaired
sperm production, infertility, abortion, weak and stillborn
young and retained placentas have all been shown to be
responsive to Se supplementation. A reduction in testicular
selenoprotein can underlie the reduced spermatogenesis or
maturation leading to the testicular atrophy associated with
Se. The mechanisms involved in Se deficiency-induced
infertility and retained placenta have not been defined
( Arthur, 1998 ; Koenig et al. , 1997 ; Smith et al. , 1987 ;
Spears, 2000 ).
As might be expected given the links to mitochondrial
function and ROS defense, altered immunocompetence has
been linked to Se deficiency. Mastitis, diarrhea, metritic,
and “ unthriftiness ” can be envisioned as being precipitated
by a reduced ability to respond to invading pathogens.
Reduction in mitogen responsiveness, phagocytotic killing
of pathogens, and antibody production have all been associated
with Se deficiency. Although the negative effects