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

VII. Zinc
687
D . Zinc Metabolism, Absorption, and
Transport
1 . Absorption
In monogastric animals, Zn is mainly absorbed from the
duodenum, jejunum, and ileum, with little being absorbed
from the stomach. In cattle, about one-third of the Zn is
absorbed from the abomasums. In most species, the initial
absorption of Zn is about 10% to 20% ( Cousins, 1998 ;
Liuzzi and Cousins, 2004 ; Cousins et al. , 2006; Sekler
et al. , 2007) . Phytate (myoinositol hexaphosphate), which
is found in all plant seeds and most roots and tubers, can
significantly inhibit Zn absorption in many species and in
humans by forming insoluble complexes. The consumption
of high phytate diets has been linked to the induction of Zn
deficiency, but usually in situations wherein the diets are
marginal in Zn content.
Similar to other trace elements, a number of dietary
constituents can influence Zn availability. High dietary iron
decreases Zn absorption, although its significance with
regard to overall Zn balance can be questioned. Several
amino acids form Zn complexes with high stability constants,
and it has been suggested that such complex formation
facilitates Zn uptake ( Cousins et al. , 2006 ; Liuzzi and
Cousins, 2004 ; Sekler et al. , 2007) . Zn absorption is higher
in neonates than in adults and is increased in Zn deficiency
in rats and cattle.
2 . Transport
Zn travels across the brush border via carrier-mediated
processes ( Fig. 22-4 ). Active transport dominates at low or
normal intake, whereas passive diffusion contributes more
significantly at high intake. The mechanisms underlying
the regulation of Zn absorption have long remained elusive.
Low-molecular-weight cellular proteins, such as metallothionein
(MT), bind Zn, Cu, and cadmium. Zn induces MT,
but only at very high intakes. The Zn transporter 1 (ZnT-1)
appears to be involved in the export of Zn across the enterocyte
basolateral membrane, whereas ZnT-2 and ZnT-4
are involved in the flux of Zn in the endosomes, possibly
regulating intracellular trafficking of Zn. ZnT-1 is localized
to the basolateral membrane, and ZnT-2 is found in acidic
vesicles that accumulate Zn ( Cousins, 1998 ; Liuzzi and
Cousins, 2004 ; Cousins et al. , 2006; Sekler et al. , 2007) .
These transporters are found primarily in villus cells and
much less frequently in crypt cells. The ileum is the major
site for ZnT-1. ZnT-2 is found in the duodenum and jejunum,
and ZnT-4 in all parts of the small intestine.
Regarding cellular uptake, in contrast to cellular
egress and intracellular organelle transport, a superfamily
of human Zn transport proteins has been identified (Zn
importer proteins, ZIP1 and ZIP2, plus others that constitute
a large family of proteins). These proteins are localized
in the plasma membrane and have structural characteristics
typical of other transport proteins (e.g., permeable membrane
domains, a transport channel, high-affinity binding
domains).
E . Zinc Deficiency
An early effect of severe Zn deficiency in many species is
anorexia and cyclic feeding. Regardless of the direct biochemical
explanation for the anorexia, the cyclical food
intake patterns of Zn-deficient animals can represent an
adaptation of the animal to the Zn-deficient diet, because
during the periods of low food intake there will be substantial
muscle catabolism and release of Zn into the plasma
pool ( Keen et al. , 2003 ; Park et al. , 2004 ; Watson, 1998 ).
Hepatic and extrahepatic tissues for Zn-requiring processes
can then use this released Zn.
If the period of Zn deficiency is prolonged, additional
hallmarks of Zn deficiency are decreased efficiency of food
utilization, impaired growth, and severe dermatitis. The
dermatological lesions are frequently characterized histopathologically
as parakeratosis. The biochemical lesions
that underlie these pathologies have not been firmly identified,
although it is recognized that a reduction in cell division
is an early event with Zn deficiency. The reduction in
cell replication in Zn deficiency has been related to the role
of Zn in nucleic acid synthesis, protein synthesis, nucleotide
transport, chromatin condensation, and assembly of
mitotic spindle via condensation, and assembly, in addition
to affecting cell cycle-related regulation and oxidative
stress (Clegg et al. , 2006; Oteiza and Mackenzie, 2005 ).
Zn responsive dermatosis is a well-documented disease
in dogs and can be manifested as two syndromes ( White
et al. , 2001 ). Syndrome I occurs primarily in northernbreed
dogs (Alaskan malamute, Samoyed, and Siberian
husky), but it has been documented in other breeds as well.
Although these dogs are generally consuming Zn-adequate
diets, they frequently require Zn supplementation, either
orally or parenterally, in some cases, for life ( White et al. ,
2001 ). Syndrome II occurs in young dogs consuming diets
that are not adequate in Zn or contain high concentrations
of calcium or phytates. Changing the dog to a Zn-adequate
diet is the only treatment necessary in most cases, along
with transient Zn supplementation.
Because of the diverse roles of Zn in nucleic acid and
protein synthesis and in gene expression, a Zn deficiency
during early development is teratogenic in mammals. Typical
malformations associated with Zn deficiency include cleft
lip and palate, brain and eye malformations, and numerous
abnormalities of the heart, lung, skeletal, and urogenital systems
( Keen et al. , 2003 ).
In addition to a high incidence of early postnatal death,
marginal Zn deficiency has been associated with altered
skeletal development and behavioral abnormalities (Ganes
and Jheon, 2004; Keen et al. , 2003 ).