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

IV. Manganese
677
IV . MANGANESE
A . Manganese Distribution
A large animal can contain from 10 to 20 mg (182 to 364
micromole) of Mn, which is fairly uniformly distributed
throughout the body. There is relatively little variation
among species with regard to tissue Mn concentrations
( O’Dell and Sunde, 1997 ). Bone, liver, and kidney tend to
have higher concentrations (1 to 3 microgram/g; 18 to 2 to
54.6 micromole/g) than other tissues. Manganese in brain,
heart, lung, and muscle is typically less than 1 microgram/g
(18.2 micromole/g); blood and serum Mn levels are
about 0.01 microgram/ml (0.182 micromol/l) and 0.001
microgram/ml (0.0182 micromol/l), respectively.
Expressed as a percentage of the total, skeletal Mn can
account for up to 25% of the total body pool. Bone Mn can
be raised or lowered by substantially varying dietary Mn,
but skeletal pools of Mn exchange slowly; thus, they are
not thought to constitute an important pool for rapid mobilization
( Reilly, 2004 ). Regarding development features of
Mn metabolism, the fetus does not normally accumulate
liver Mn before birth, and the levels of Mn in fetal liver
are lower than in adult liver. This appears to be due to the
expression of Mn enzymes such as arginase, pyruvate carboxylase,
and MnSOD that occurs predominantly after
birth ( Bourre, 2006 ; Keen et al. , 1999 ).
B . Manganese Function
Mn functions both as an enzyme activator and as a constituent
of metalloenzymes. For Mn-activated reactions, it
can act by binding either to a substrate (such as ATP) or
to the protein directly, to facilitate subsequent conformational
changes. Whereas there are relatively few Mn metalloenzymes,
there are a large number of enzymes that can
be activated upon Mn additions (e.g., various hydrolases,
kinases, decarboxylases, and transferases). Although the
extent to which such activation is specifically related to Mn
can be questioned (e.g., Mg can replace Mn), some appear
Mn specific (e.g., several glycosyltransferases). Other divalent
cations do not readily activate glycosyltransferases, and
some of the pathological defects associated with Mn deficiency
can be ascribed to a low activity of enzymes in this
classification (Bourre, 2006 ; Keen et al. , 1999 ). For example,
it has been suggested that xylosyl transferase is specifically
activated by Mn. Cartilage isolated from Mn-deficient
chicks is xylose poor, and fetuses born of Mn-deficient rats
have limb deformities that can be related to reduced glycosylation
(Lui et al. , 1994). In addition, Mn can activate
phosphoenolpyruvate carboxykinase in vivo ; low activity
of phosphoenolpyruvate carboxykinase has been reported
in Mn-deficient rats. Other Mn-containing and sensitive
enzymes include arginase, pyruvate carboxylase, MnSOD,
and glutamine synthase. All except glutamine synthase have
been reported to be low in Mn-deficient animals ( Aschner
and Aschner, 2005 ; Crossgrove and Zheng, 2004 ; Ensunsa
et al. , 2004 ; Spears, 2003 ) .
C . Dietary Manganese
Nutritional Mn deficiency occurring outside the laboratory
has been documented in a number of species including cattle,
chickens, and rats. In humans, abnormal Mn metabolism
has been reported to be a potential problem in epilepsy,
Down’s syndrome, osteoporosis, and diabetes (Aschner and
Aschner, 2005; Crossgrove and Zheng, 2004 ; Spears, 2003 ).
The recommended daily requirements for Mn for a number
of species are shown in Table 22-2 . Diets containing less
than 1 micrograms Mn/g (0.018micromol/g) are unable to
support normal reproduction in several species (i.e., sheep,
goats, cattle, pigs, mice, rats, and rabbits). For perspective,
the maximum reproductive performance in cattle does
not occur until diets contain more than 20 micrograms Mn
(0.31 micromol) per gram diet on a dry weight basis. The
minimum dietary Mn requirement for poultry for growth
and normal egg production and hatchability is about 40
micrograms/g (0.73 micromol/g) under normal dietary conditions.
Excess dietary fiber, calcium, and phosphorus can
markedly increase Mn requirements by reducing Mn bioavailability.
The higher Mn requirements of birds compared
to mammals can be due to a lower efficiency of absorption
( Hansen et al. , 2006 ; Miranda et al. , 2006 ; Nocek
et al. , 2006 ; Subcommittee on Mineral Toxicity in Animals,
1980; Subcommittee on Poultry Nutrition, 1994; Weis and
Socha, 2005). Food items considered high in Mn include
nuts, whole cereals, dried fruits, and leafy vegetables.
Meats, dairy products, poultry, and seafood are considered
to be poor sources of Mn. Manganese in typical animal
feeds can range from 10 microgram/g (0.18 micromol/g) in
corn to 105 microgram/g (2.73 micromol/g) in ryegrass and
red clover, with the concentration highly dependent on soil
conditions and fertilizer practice.
D. Manganese Metabolism, Absorption,
and Transport
Absorption of Mn is thought to occur throughout the small
intestine. The efficiency of Mn absorption is relatively low
and is not thought to be under homeostatic control ( Keen
et al. , 2000 ; Sandstrom, 2001 ). It has been reported that
adult humans typically absorb approximately 3% to 4% of
dietary Mn, although absorption is increased in those with
iron deficiency. High dietary intakes of dietary calcium,
phosphorus, and phytate can increase requirements for Mn.
Mn absorption and retention are higher in neonates than in
adults, and it has been suggested for this reason neonates
can be particularly susceptible to Mn toxicosis ( Keen et al. ,
2000 ). The overall health status of the animal can also