healthy dogs and biomarkers of zinc status. To ensure an adequate zinc status, it is important to know

Overview

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Key numbers

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R. Jorge Viterbo Ferreira nº 228, 4050-313 Porto, Portugal; anamargaridabp@hotmail.com (A.M.P.);
Animals 2021, 11, 978. https:// consequence or the cause. This review presents data on zinc requirements and biomarkers for zinc
doi.org/10.3390/ani11040978 status, that can be applied for the development of supplementation strategies of zinc in complete pet
published maps and institutional affil- portance of zinc for the metabolism of microorganisms was discovered in 1866 when Jules
iations. Raulin confirmed its essentiality for the growth of Aspergillus niger (1). However, its essen-
tiality for mammals was only recognized in 1934 for rats (2), in 1961 for humans (3), and in
1962 for dogs (4). Under physiological conditions, the dogs’ access to zinc depends upon
Attribution (CC BY) license (https:// In dogs, the role of zinc in skin health has been well documented (14–16). Besides, clinical
4.0/). systems. However, to fully comprehend the mechanisms that link zinc to the clinical signs
Animals 2021, 11, 978. https://doi.org/10.3390/ani11040978 https://www.mdpi.com/journal/animals
Animals 2021, 11, 978 2 of 26
1. Overview of Zinc Homeostasis and Metabolism
Zinc is predominantly distributed intracellularly (50% in the cytoplasm, 10 to 20% in
mitochondria, endoplasmic reticulum, and Golgi apparatus) (17), serum zinc only constitut-
ing a small fraction (0.1%) of whole-body zinc (18). Both zinc cellular influx and efflux are
increases cellular zinc (19). Moreover, ZnT and ZIP are responsible for transporting zinc
between cytosol and intracellular organelles/vesicles (17). In mammals, 10 ZnT and 14 ZIP
ments, apart from ZnT1 that is ubiquitous at plasmatic membranes, whereas the location
of ZIP proteins may vary according to zinc availability and physiological conditions (20).
physiological conditions (21). In this way, MT participates in the regulation of intracellular
storage and release, respectively, when zinc is required or depleted (21). Both MT and
other key proteins, such as ZnT1, are controlled by the metal-response element-binding
transcription factor-1 (MTF-1), which acts as a cellular zinc sensor (22). Figure 1 illustrates
zinc homeostasis in mammals can be found elsewhere (17,23,24).
site in dogs, the duodenum, followed by the distal ileum and proximal jejunum (25). The
located at the apical membrane (21). To a small extent, zinc absorption can occur via
basolateral transport, particularly in the presence of high luminal concentrations (21).
Carrier proteins may also uptake zinc as chelates (26).
ZIP 4, ZIP 5, ZnT1, and ZnT7 (21). ZIP4 is essential for the uptake of dietary zinc in
the apical membrane. After uptake, zinc is transferred to the portal blood by ZnT1 on
expression of ZIP4 in cells at a posttranslational level (27). Although no data is available in
abundance of MT in groups fed a high concentration of zinc (2425 mg/kg) comparing
to low (57 mg/kg) and adequate (164 mg/kg) groups, which did not differ from each
other (28). Moreover, in the study of Martin et al., the group fed low zinc had decreased
Animals 2021, 11, 978 3 of 26
each other (28). This transporter is present in vesicles and secretory glands in the small
intestine and other organs, e.g., kidney, liver, pancreatic acinar cells (18), also contributing
to zinc homeostasis and responding to dietary zinc. ZnT7, which is present in enterocytes
the trans-Golgi network, after endocytosis (21). In mice, ZnT7 was found important for
unresponsive to increases in dietary zinc (29). Besides being transported into organelles,
Animals 2021, 11, x FOR PEER REVIEW 3 of 28
zinc can be bound to cytoplasmic-binding proteins, such as MT (21).

Methods (brief)

samples analyzed, and the results were rarely presented according to age category. Five
analyzed 49 wet samples from different brands and found that the content of zinc in wet
that both nutritional requirements and legal impositions were respected in all samples
samples both for puppies, adult, and senior dogs, mainly commercialized in the United
samples analyzed, and the results were rarely presented according to age category. Five
analyzed 49 wet samples from different brands and found that the content of zinc in wet
that both nutritional requirements and legal impositions were respected in all samples (75).
content in bone and raw food rations, reported that more than half of the samples analyzed
ligand with high-chelating zinc capacity, resists peptide digestion, and thus, prevents the
to ejaculates collected from dogs, had a positive effect on the sperm plasma membrane and
1. Martin, L.; Lodemann, U.; Bondzio, A.; Gefeller, E.-M.; Vahjen, W.; Aschenbach, J.R.; Zentek, J.; Pieper, R. A High Amount of
1. Butterwick, R.F.; Erdman, J.W., Jr.; Hill, R.C.; Lewis, A.J.; Whittemore, C.T. Challenges in developing nutrient guidelines for
1. Kelly, D.G.; White, S.D.; Weir, R.D. Elemental composition of dog foods using nitric acid and simulated gastric digestions. Food
1. Uchida, Y.; Moon-Fanelli, A.A.; Dodman, N.H.; Clegg, M.S.; Keen, C.L. Serum concentrations of zinc and copper in bull terriers

Implications

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Update history

The five most recent substantive edits to this page, classified major (evidence or structure moved), correction (a published value or statement was wrong and has been fixed), or minor (narrative rewritten without changing the underlying evidence). Each description is derived from what the edit did to this page; the linked commit is the authoritative record, routine regeneration passes are excluded, and the full version history lives in git. When DOI minting comes online (see schema docs), each entry below will also link to a version-pinned DataCite DOI.

Commit	Date	Change	Description
3171d06	2026-08-02	major	1 section added
bc84bfc	2026-08-02	major	6 sections added; narrative text revised