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

II. Cobalt
667
TABLE 22-3 Potential Causes of Trace Element
Deficiencies
Cause
Food processing
Dietary interactions
Drug interactions
Disease or genetic
Mechanism
Loss of elements because of refining
Competitive interactions between
elements
Impaired absorption or increased
excretion; redistribution of elements
among tissue pools; decreased
absorption (chelators, laxatives);
increased excretion (diuretics)
Increased requirement because of
a block in the normal metabolism
of the element (primary); increased
requirement because of decreased
absorption or increased excretion
secondary to the disorder (secondary)
In tissues, Co is normally found associated with vitamin 12
or cobalamin in all animals that require preformed vitamin
B 12 . Cobalt in most tissues is low (picomolar concentrations),
with liver, heart, and bone containing the highest tissue
levels. Low normal serum cobalamin is approximately
2 to 3ng cobalamin/ml (1.5 to 2.3 nmol/liter). In contrast to
Zn, Cu, and Fe, Co does not accumulate with fetal age and
it is not stored to any appreciable degree in the adult animal
( Ammerman and Goodrich, 1983 ; Keen, 1996 ). With toxicity,
tissue Co can increase over 10-fold in cattle ( Barceloux,
1999 ; Domingo, 1989 ; Lauwerys and Lison, 1994 ).
A. Cobalt Function
Cobalt is novel because there is no evidence that any organism
needs the cobalt ion, either in the free form or as a simple
protein complex. Cobalt in the form of a specific complex,
vitamin B 12 or one of the cobalamides, is essential for animals
and many bacteria. Plants contain cobalt, but there is no
evidence that it occurs as a cobalamide. Vitamin B 12 is also
unique among vitamins in that plants do not produce it.
The role of rumen microflora in the economy of ruminant
animals makes ionic cobalt of particular significance to this
group of animals. Although one cannot dismiss the possibility
that some organisms require cobalt other than that in
a corrinoid (B 12 -related) complex, there is no such evidence
at present and this discussion will hinge primarily around
the metabolism and metabolic function of cobalt as it exists
in the cobalamides. In aqueous solution, Co is generally in
the 2 or 3 oxidation state. Cobaltous ion forms complexes
with both octahedral and tetrahedral geometry ( Burgess,
1999 ; Kerber and Goldberg, 2006 ). All Co complexes are
octahedral and most involve nitrogen as the electron donor.
The skeletal structure of the cobalamides can be visualized
by representing the corrin ring of cobalamides with a planar
ring and the ligands by X and Y (see Chapter 23) . Both the
cobalamides and cobaloximes (simpler cobalt corrin-like
structures) act as the catalytic site for intramolecular mutations
and single carbon transfer reactions ( Frausto da Silva
and Williams, 1991 ). Such reactions are important to tissue
and cellular growth; as such, Co is primarily associated with
erythropoiesis, granulopoiesis, and glucose homeostasis. Two
important enzymes that require vitamin B 12 as a cofactor are
(1) methylmalonyl-CoA mutase, which catalyzes the molecular
rearrangement of methylmalonyl-CoA to succinyl-CoA:
O 2 C
H
OH
O 2 C
H
OH
H
H
H
H
CO 2
Ad
H
H
H
H 3 C
CO 2
Co
O 2 C
H
H
H
OH
H
CO 2
Ad
H
Co(II)
H
H
O 2 C
H
H 2 O
H
OH
CO 2
slow step
O 2 C
H
H
OH
H
H
CO 2