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

668
Chapter | 22 Trace Minerals
P i PP i
substrates
CH 3 -substrates
ATP
S-adenosyl methionine
methionine
S-adenosyl homocysteine
B 12
homocysteine
N 5 -methyl THE
adenosine
THF
and (2) 5 -methyltetrahydrofolate-homocysteine methyltransferase,
which demethylates 5 -methyltetrafolate and
regenerates methionine and tetrahydrofolate.
The former reaction is critical for glucose homeostasis
in ruminants because a primary gluconeogenic precursor
for these animals is propionic acid. Because propionic acid
has three carbons, propionyl-CoA cannot enter b-oxidation
nor the citric acid cycle; thus, in most vertebrates it is
carboxylated to D-methylmalonyl-CoA, isomerized to
L-methylmalonyl-CoA, and rearranged to yield succinyl-
CoA via the vitamin B 12 -dependent step shown previously.
Succinyl-CoA is an intermediate of the citric acid cycle
and can be readily incorporated there.
Another aspect of Co in mammalian systems is the
potential pharmacological effect of high doses of Co on
erythropoietin production ( Katsuoka et al. , 1983 ). Whether
physiological concentrations of Co influence erythropoietin
production is not known. Dietary requirements (as
B 12 ) in most animals are usually met either by ingestion
of animal tissues or products or by coprophagy. Because
of the rumen microflora, ruminants can be fed ionic Co,
and the microbes will synthesize cobalamin for absorption.
Nevertheless, the relative inefficiency of vitamin B 12 production
in the rumen and poor absorption of B 12 predispose
ruminants to deficiency. Between 2 and 5 mg/day (1.5 to
3.9 μ mol/day) of CoCl for sheep and 20 to 30 mg/day (15.4
to 23.1 μ mol/day) for cattle are required for normal B 12
production ( Kennedy et al. , 1995 ; Kincaid et al. , 2003 ) .
B . Absorption and Transport
In rats, 80% of orally administered Co appeared in the
feces. High amounts of iron in the diet can depress Co
absorption and vice versa. Co absorption is enhanced in
iron deficiency ( Domingo, 1989 ). Excretion of Co is primarily
via the kidneys and is linearly related to the ingested
dose. Additional sites of excretion have been reported to be
the large intestine in chicks and the bile and small intestine
in mammals.
Absorption of vitamin B 12 depends on normal gastric
parietal cell synthesis of intrinsic factor and a healthy
ileal mucosa for the binding and transport of the vitamin
B 12 . Response to therapy and a ration containing less than
0.08 mg Co/g (1.4 μ mol/g) of diet is diagnostic of Co deficiency
in ruminants. In sheep, hepatic vitamin B 12 levels
of less than 0.1 μ g/g (0.07 n mol/g), or serum levels of less
than 0.3 ng/ml (0.2 nmol/liter), are associated with impending
or frank deficiency. Thus, vitamin B 12 status can be
used to assess Co adequacy in sheep. Although measurement
of plasma cobalamin levels has been considered sufficient
for assessment of Co status in sheep, it has been
suggested that liver cobalamin should also be included in
assessment studies as plasma levels do not always reflect
soft tissue levels ( Mills, 1987 ). In this regard, it should be
considered that the measurement of plasma cobalamin is
complicated by the presence of cobalamin analogues that
interfere with the assay ( Halpin et al. , 1984 ). Therefore,
the measurement of plasma methylmalonate levels is
used as an indirect indicator of the functional cobalamin
status of the animal. The increase in methylmalonate
is due to a reduction in the activity of mehylmalonyl-
CoA mutase, for which adnosylcobalamin is a cofactor
(discussed earlier).
C . Disorders of Cobalt Metabolism
The signs and biochemical lesions that are manifested in
Co deficiency are referable to a deficiency of vitamin B 12 .
The pathways that are most severely impaired are those of
purine biosynthesis and glucogenesis. Deficiencies of Co
have been correlated with a reduction in blood glucose and
an increase in methylmalonic acid excretion. A primary
defect in Co deficiency underlying the previous discussion
has been attributed to a reduction in the activity of