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

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Chapter | 22 Trace Minerals
tissue Mn concentration. Caution must be exercised in
interpreting serum Mn values, however, because they can
reflect recent dietary history rather than the long-term Mn
status of the animal ( O’Dell and Sunde, 1997 ). Although
measurement of hair Mn has been used as an indicator of
Mn status, most investigators agree that the value of this
analyte is limited owing to excessive environmental contamination
with Mn ( Bouchard et al. , 2007 ). Liver Mn concentrations
have been used as an indicator of Mn status in
animals, but their main value is in the identification of Mn
deficiency conditions. Currently there are no satisfactory
laboratory tests for the identification of Mn toxicity ( Reilly,
2004 ), although high levels of tissue Mn can be assessed
with imaging techniques, such as MRI ( Jiang et al. , 2007 ).
V . MOLYBDENUM
A . Molybdenum Distribution
The highest concentrations of Mo are in the liver (0.5 to
0.7 μ g/g) and kidney (0.3 μ g/g). In sheep, whole blood
Mo is about 0.02 μ g/ml (0.21 μ mol/liter) but is sensitive
to changes in dietary intake ( Spears, 2003 ; Suttle, 1991 ).
The most important function is as a cofactor for xanthine
dehydrogenase/oxidase, aldehyde oxidase, and sulfite oxidase.
Mo is present in these enzymes as molybdopterin
or a molybdenum cofactor ( Fig. 22-5 ). Xanthine oxidase
was first characterized as a Mo enzyme in the early 1950s
( Mendel and Bittner, 2006 ; Schwarz and Mendel, 2006) .
B . Molybdenum Functions
In its usual form as xanthine dehydrogenase, the reaction,
XH H 2 O NAD → X O NADH, is catalyzed. The
most common substrates are purines. Uric acid forms the
metabolic endpoint of purine degradation. The last metabolic
steps in the process (from hypoxanthine to xanthine
and from xanthine to uric acid) are promoted by xanthine
dehydrogenase (oxidoreductase, EC1.1.3.22). The overall
mechanism is complex. Xanthine dehydrogenase is a flavoprotein
that contains both iron and Mo and uses NAD
as electron acceptor ( Mendel and Bittner, 2006 ; Schwarz
and Mendel, 2006) .
Moreover, xanthine dehydrogenase exists in two interconvertible
forms, xanthine dehydrogenase and xanthine
oxidase. In its oxidase form, the enzyme transfers the
reducing equivalent generated by oxidation of substrates to
molecular oxygen with the resultant production of superoxide
anion and hydrogen peroxide ( Fig. 22-3 ). Hydrogen
peroxide can be converted to free hydroxyl radicals. For
example, during ischemia, reperfusion, or reoxygenation
of an injured tissue can occur, and xanthine dehydrogenase
can be converted to xanthine oxidase ( Mendel
and Bittner, 2006 ; Schartz, 2005) . In this latter form, the
reaction sequence is XH H 2 O O 2 → X O H 2 O 2 .
Given that in such conditions ATP is depleted and there is
an increase in the purine pool, such available substrate promotes
production of large quantities of superoxide radicals
are released, which can be a major source of tissue peroxidation.
Aldehyde oxidase is a related Mo enzyme that
catalyzes many of the same reactions as xanthine dehydrogenase.
Both of these enzymes are needed in ruminants to
catabolize exogenous pyrimidines. The third known Mo
enzyme is sulfite oxidase, a mitochondrial enzyme that
catalyzes the oxidation of sulfite to sulfate during the degradation
of sulfur amino acid ( Mendel and Bittner, 2006 ;
Schwarz and Mendel, 2006) .
C . Molybdenum Metabolism, Absorption,
and Transport
Other than thiomolybdates, Mo is well absorbed by all species.
It has been proposed that Mo is transported by a carriermediated
process and that sulfate and Mo can compete for
the same carrier or inhibit membrane transport in the intestine
and renal tubules ( Brondino et al. , 2006 ; Failla, 1999 ;
Spears, 2003 ), hence impairing Mo absorption and retention.
An alternate postulate is that formation of insoluble
thiomolybdates precludes absorption. Cu and sulfur influence
Mo absorption. High dietary levels of vitamins E and
C, zinc, iron, tungsten, and dietary protein levels can also
affect optimal status. Cu or sulfur reduces Mo availability
via a mechanism whereby reactive sulfides or hydrogen
sulfide ions displace oxygen in molybdate to form thio- and
oxythiomolybdates (see Section III) ( Spears, 2003 ; Suttle,
1991 ). This complex can in turn react with Cu to form
an insoluble complex. This is primarily applicable to the
strong reducing environment of the rumen. Because of this
interaction, excess Mo will induce a secondary Cu deficiency
(e.g., dietary Mo in excess of 10 μ g/g; 0.104 μ mol/
g; Johnson et al. , 2007 ; Spears, 2003 ; Suttle, 1991 ).
Excretion in nonruminants appears to be mostly
through the urine, but in ruminants fecal and milk losses
can represent significant losses. Although Mo deficiency
does occur, it is apparently relatively rare. In animals,
growth and production have been reported to be impaired
in poultry and sheep ( Suttle, 1991 ). In the case of birds, the
high flux of metabolites through purine-related pathways
accounts in part for the need for Mo (e.g., as a cofactor
for xanthine oxidase). For the ruminant, one postulate has
been a depression in microbial Mo enzyme activities.
The clinical syndrome of Mo toxicity can be characterized
by achromotrichia, anemia, cartilaginous dysplasia,
abnormal endochondrial ossification, subperiosteal ossification,
and abnormal fibrogenesis ( Spears, 2003 ; Suttle, 1991 ).
These lesions are characteristic signs of an induced Cu deficiency.
Additionally, Mo has been suggested to specifically
induce mandibular exostosis, aberrations in phosphorus
metabolism that can contribute to bone and joint lesions,
testicular degeneration, and central nervous system changes.