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

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Chapter | 22 Trace Minerals
influence absorption and its susceptibility to Mn toxicity.
Studies in poultry have demonstrated that under conditions
of duodenal coccidiosis Mn is utilized more efficiently.
Coccidial infection exacerbated Mn toxicity as evidenced
by depressed hematological parameters and increased bone
and bile Mn concentrations ( Southern and Baker, 1983 ).
In contrast to other essential trace elements, Mn
absorption does not appear to be increased under conditions
of Mn deficiency ( Keen et al. , 2000 ). Mn absorption
is increased under conditions of Fe deficiency. Because of
the connection between the transport of iron and Mn, the
transferrin receptor (TfR) and the divalent metal transporter-1
(DMT-1) seem to play a role in Mn transport,
which could be the basis for the connection (Aschner and
Aschner, 2005; Culotta et al. , 2005 ; Keen et al. , 2000 ). Mn
from the gastrointestinal tract entering the portal blood can
either remain free or rapidly becomes bound to alpha-2-
macroglobulin and transferrin, particularly as Mn 3 . Mn
uptake by cells is usually unidirectional and saturable.
The metabolic fate of newly absorbed Mn entering the
hepatocyte has not been well defined, although several cellular
pools of Mn can be identified. The first represents Mn
taken up by the lysosomes. Lysosomal uptake of Mn is also
considered to be an essential step to egress as it is thought
that lysosomes concentrate Mn for delivery to the bile canaliculus
(i.e., whole body homeostatic regulation of Mn is
maintained through biliary excretion). In this regard, up to
50% of Mn injected intravenously can be recovered in the
feces within 24 h. Another pool of Mn is associated with
the mitochondria. Mitochondria have a large capacity for
Mn 2 uptake, and it has been suggested that mitochondrial
Mn 2 and Ca 2 uptake can be linked. Nuclear, cytoskeletal
(microsomal), and cytosolic pools of Mn 2 also exist. In
contrast to Zn, Cu, and Fe for which only a few atoms per
cell exist in free form, a portion of Mn can be viewed as
dissociable, somewhat analogous to Ca 2 and Mg 2 ( Keen
et al. , 2000 ).
E . Deficiency and Excesses
1 . Defi ciency
Manifestations of Mn deficiency in domestic animals
include impaired growth, skeletal abnormalities, disturbed
or depressed reproductive function, ataxia of the newborn,
and defects in lipid and carbohydrate metabolism ( Keen
et al. , 2000 ). Biochemical lesions associated with these
defects are discussed later.
The effects of Mn deficiency on skeletal development
have been reported extensively. Mn deficiency results in
limbs that are shortened and thickened and joints, which
are swollen and enlarged (Lui et al. , 1994 ). Multiple
reports of Mn deficiency in cattle are also present in the literature.
One interesting case describes 47 Holstein calves
with dwarfism, joint laxity, superior brachygnathism, and
domed foreheads that were born to heifers grazing naturally
on one farm in South Africa. Seepage from seawater
evaporation pans on an adjacent farm was believed to cause
Mn deficiency in the dams by leaching Mn from the soil.
The seawater contained high levels of strontium, calcium,
and iron, which likely further inhibited Mn absorption
( Staley et al. , 1994 ). As noted earlier, a basic biochemical
lesion underlying the development of bone defects with
Mn deficiency is a reduction in proteoglycan biosynthesis,
which is secondary to a reduction in the activities of glycosyltransferases.
These enzymes are specifically activated
by Mn and are needed for the synthesis of chondroitin sulfate
side chains of proteoglycan molecules ( Hansen et al. ,
2006) .
Ataxia in the offspring of Mn-deficient animals was first
observed in the chick and in rats in the 1940s. Ataxia is the
result of impaired vestibular function caused by impaired
otolith development in utricular and secular maculae. The
precise biochemical lesion underlying the block in otolith
development has not been identified, although it is thought
to involve a defect in proteoglycan biosynthesis. Further,
defects in carbohydrate metabolism, in addition to those
known to arise from impairment of the activities of glycosyltransferases,
have been observed in Mn-deficient rats
and guinea pigs. In the guinea pig, Mn deficiency results
in severe pancreatic pathology with aplasia or marked
hypoplasia of all cellular components including fewer and
less intensely granulated islet cells than controls. When
glucose is given either orally or intravenously to Mn-deficient
guinea pigs, they display diabetic-like glucose tolerance
curves. Mn supplementation completely reverses the
abnormal glucose tolerance. Mn deficiency can also affect
carbohydrate metabolism through an effect on insulin
metabolism ( Keen et al. , 2000 ; O’Dell and Sunde, 1997 ).
Mn associated with the islet cell exists in two pools: a
readily exchangeable pool associated with the cell surface
and an intracellular pool. Mn fluxes between these pools
can affect insulin release. Accumulation of Mn associated
with the islet cell membrane inhibits insulin release,
whereas increases in the intracellular concentration of
Mn are associated with a stimulation of insulin synthesis
or release, consistent with the idea that Mn has a regulatory
role in insulin synthesis/release. In rats, Mn deficiency
depresses pancreatic insulin synthesis and secretion, and
it enhances intracellular insulin degradation ( Keen et al. ,
2000 ).
Regarding lipid metabolism, Mn-deficient pigs, rats,
and mice are characterized by deposition of excess fat in
the liver. Abnormal lipid metabolism has been suggested
as a cause of some of the ultrastructural abnormalities seen
in tissues of Mn-deficient animals, which include alterations
in the integrity of cell membranes, swollen and irregular
endoplasmic reticulum, and elongated mitochondria
with stacked cristae. The effect of Mn deficiency on cell
membrane integrity could be due to changes in membrane