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

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Chapter | 22 Trace Minerals
be linked to specific enzymes such as Cu-Zn superoxide
dismutase (CuZnSOD), which catalyzes the dismutation
of the superoxide anion; dopamine β-hydroxylase, responsible
for noradrenalin and adrenaline production; and
melaninase, responsible for melanin production ( Keen et al. ,
2003 ; Rucker et al. , 1998 ; Stites et al. , 2000 ; Tinker and
Rucker, 1985 ).
A diverse array of physiological symptoms, particularly
during the perinatal period, can occur including hypotension,
muscle hypotonia, hypothermia, and hypoglycemia.
Moreover, elastin and collagen from Cu-deficient animals
have an elevated content of lysine and a low content of various
cross-linking amino acids. Loss of cross-linking results
in defects in the elastic properties of arteries and decreases
in bone strength and the tensile strength of various connective
tissues. A reduction in CuZnSOD can increase hydrogen
peroxide and superoxide radicals that can irreversibly
oxidize proteins, nucleic acids, lipids, and carbohydrate
components within cytoskeletal structures and the cell wall.
Changes in Cu status, particularly in the fetus and neonates,
have been associated with perturbations in nitric
oxide (NO) metabolism, a key signaling molecule to endothelial
cell responsiveness (e.g., contraction and relaxation).
Moreover, when an increase in hydroxyl radical occurs,
because of a reduction in CuZnSOD activity, the reaction
of peroxide radicals with NO can produce peroxynitrite.
Peroxynitrite, another potent oxidant, can cause ATP depletion
and peroxynitrite-induced nitration of tyrosine residues
on proteins. Many of the neurological signs and endothelial
changes associated with Cu deficiency are thought to be the
result of altered NO metabolism ( Schuscha, 1997 ; Yang
et al. , 2007 ) and peroxynitrite-induced lesions ( Fig. 22-3 ).
Other Cu-containing enzymes include tryptophan oxygenase,
ascorbate oxidase, tyrosinase, amine oxidases,
peptidyl-glycine- α -amidating monooxygenase, and possibly
some fatty acid desaturase enzymes such as C18
Δ °-desaturase. It has been suggested that Cu can also be
involved in a nonenzymatic manner in neuropeptide release
from the brain.
C . Dietary Copper
Copper absorption from diets is relatively efficient, although
some dietary constituents can affect bioavailability.
Copper hydroxides, iodides, glutamates, and citrates are
more easily absorbed than molybdates, sulfates, and phytates.
High intakes (100 or more mg/kg of diet) of Ag and
Zn can interfere with intestinal copper transport. Moreover,
the extended use of supplements that contain iron can
negatively affect copper status. Cu absorption is greater in
neonates than in adults ( Committee on Copper in Drinking
Water, 2000 ; Stern et al. , 2007 ).
Another interaction that has attracted attention involves
Cu, Mo, and sulfate. Particularly in ruminants, dietary sulfate
intensifies the harmful effects of Mo on Cu absorption.
CuSO 4 and Na 2 MoO 4 react to form an insoluble complex
referred to as a thiomolybdate, which renders Cu biologically
less active and less bioavailable (see Section V) .
Nutritional Cu deficiency occurring outside of the laboratory
has been well documented in a variety of species
including humans, cattle, sheep, pigs, and horses. The recommended
minimal daily requirements for Cu for a number
of species are presented in Table 22-2 . Given that the
uptake of Cu from a diet can be influenced by other dietary
factors as well as the physiological state of the animal,
under some conditions, a diet cannot contain sufficient Cu
for the animal even though the level of Cu in the diet is at
the level suggested in the NRC tables.
Food items that are high in Cu include nuts, dried
legumes, dried vine, and dried stone foods (300 to 400 μ g/g;
4.72 to 6.30 μ mol/g). Food items considered low in Cu
content ( 1 μ g/g; 0.016 μ mol/g) include dairy products
and sugar, refined cereals, fresh fruits, and nonleafy vegetables
contain about 7 μ g Cu/g (0.11 μ mol/g). Copper in
typical animal feeds can range from 20 μ g/g (0.315 μ mol/g)
(cottonseed meal) to 2 (0.032 μ mol/g) (corn), with the concentration
being highly dependent on soil conditions and
fertilizer practices.
D . Copper Metabolism, Absorption, and
Transport
1 . Cellular Transport and Regulation
Copper is absorbed in all segments of the gastrointestinal
tract. For most species, absorption occurs in the upper
small intestine, but in sheep considerable absorption also
occurs in the large intestine. Absorption of Cu is about 30%
to 60% with a net absorption of about 5% to 10% owing
to the rapid excretion of newly absorbed Cu into the bile.
A delicate balance between Cu uptake and efflux maintains
copper homeostasis ( Cromwell et al. , 1989 ; Gooneratne
et al. , 1989 ; O’Dell and Sunde, 1997 ; Reilly, 2004 ; Stern
et al. , 2007 ; Theile, 2003).
Cu uptake occurs through both high- and low-affinity
transport systems ( Fig. 22-4 ). Environmental factors can
influence the response to transporters. Most important are
factors that influence solubility and redox state. Cu exists
in two different valence states; the cupric ion (Cu 1 ) is the
primary substrate for the transport systems that take Cu
across plasma membranes. Reduction (Cu 2 → Cu 1 ) is
catalyzed by plasma membrane reductases (Theile, 2003).
However, the cuprous ion (Cu 2 ) in the intestinal lumen is
more soluble than the cupric ion (Cu 1 ). Chemical reduction
of luminal contents (e.g., by reducing agents such as
ascorbic acid) can decrease the amount of Cu that is bioavailable
(i.e., affectively delivered to the surface of intestinal
cells). It is important, however, to note several caveats.
Observations in humans suggest that the effects of ascorbic