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Byrne, L.;  Murphy, R.A. Trace Minerals in Animal Nutrition. Encyclopedia. Available online: https://encyclopedia.pub/entry/27438 (accessed on 28 July 2024).
Byrne L,  Murphy RA. Trace Minerals in Animal Nutrition. Encyclopedia. Available at: https://encyclopedia.pub/entry/27438. Accessed July 28, 2024.
Byrne, Laurann, Richard A. Murphy. "Trace Minerals in Animal Nutrition" Encyclopedia, https://encyclopedia.pub/entry/27438 (accessed July 28, 2024).
Byrne, L., & Murphy, R.A. (2022, September 21). Trace Minerals in Animal Nutrition. In Encyclopedia. https://encyclopedia.pub/entry/27438
Byrne, Laurann and Richard A. Murphy. "Trace Minerals in Animal Nutrition." Encyclopedia. Web. 21 September, 2022.
Trace Minerals in Animal Nutrition
Edit
This entry is adapted from the peer-reviewed paper 10.3390/ani12151981

Trace mineral refers to the nutritional elements added to production and companion animal diets in micro quantities. They are involved in structural, physiological, catalytic, and regulatory functions in animals. The importance of dietary supplementation of animal feeds with trace minerals is irrefutable, with various forms of both organic and inorganic products commercially available.

organic trace mineral (OTM) copper iron manganese zinc animal production

1. Introduction

“Trace mineral” is the term used to describe nutritional elements added to production and companion animal diets in micro quantities [1]. They are involved in structural, physiological, catalytic, and regulatory functions in animals and their inclusion in animal diets is necessary for a multitude of reasons. Diets may not contain adequate amounts of specific minerals to meet animal requirements, minerals in feed may not be in a form that is biologically available, or anti-nutritional factors may reduce the total proportion of the nutrient in a feedstuff that is available for use in normal body functions. Furthermore, mineral requirements vary over the lifecycle of the animal and tailored supplementation strategies are paramount to obtain optimum results in modern animal production systems. Of the trace minerals commonly included in dietary formulations, four were selected here: copper, iron, manganese and zinc. Table 1 outlines the primary function of each of the aforementioned minerals, highlighting their importance in animal diets. Marked deficiencies are unlikely to occur in modern commercial production systems; however, marginal deficiencies could occur under certain conditions such as poor feed formulation or low feed intake. The occurrence and severity of mineral deficiencies are influenced by length of time that deficient diets are fed, prior mineral status, and physiological state [2].
Table 1. Primary functions and inclusion levels of selected trace minerals and signs of deficiency.
Mineral Function Signs of Deficiency EU Maximum Inclusion Levels: Maximum Content of Element in mg kg−1 of Complete Feed with a Moisture Content of 12%
Copper Involved in metabolic reactions including cellular respiration, tissue pigmentation, haemoglobin formation (caeruloplasmin) and connective tissue development [3][4]. Essential component of several metalloenzymes [5][6]. Protects against oxidative stress [6][7]. Muscle weakness, iron-deficient anaemia, hypopigmentation, bone changes resembling scurvy, defective connective tissue synthesis, hair abnormalities, impaired myelinisation of nerve tissues and neurological defects, altered lipid metabolism and cardiac malfunction [8][9][10]. Bovines: Bovines before the start of rumination: 15 (total), Other bovines: 30 (total)
Ovines: 15 (total)
Caprines: 35 (total)
Piglets: Suckling and weaned up to 4 weeks after weaning: 150 (total), from 5th week after weaning up to 8 weeks after weaning: 100 (total)
Crustaceans: 50 (total)
Other animals: 25 (total) [11]
Iron Important for physiological function—haemoglobin, in which the heme portion functions to carry oxygen from the lungs to the tissues, mitochondrial Fe enzymes essential for oxidative production of cellular energy through Krebs cycle, transport of oxygen by myoglobin to cells and tissue of muscle. Important for immune function and lipid metabolism. Supressed growth and blood volume [12]. Decreased animal performance, loss of appetite and weight, spasmodic breathing and ultimately death [13]. Ovine: 500 (total (1)), Bovines and poultry: 450 (total (1))
Piglets up to 1 week before weaning: 250 mg/day (total (1))
Pet animals: 600 (total (1)) Other species: 750 (total (1)) [14]
Manganese Constituent of multiple enzymes. Component of the organic matrix of bone and is essential for cartilage development. Involved in the metabolism of calcium and carbohydrates. Necessary for the utilisation of biotin, vitamin B1 and vitamin C [15]. Metabolic association between manganese and choline which affects fat metabolism in the liver [16]. Impaired growth, skeletal abnormalities, abnormal reproduction function, ataxia in newborns, impaired carbohydrate and lipid metabolism and impaired mucopolysaccharide synthesis [17]. Poultry specific issues include: Perosis (slipped tendon), thin eggshell quality, chondrodystrophy in embryonic chicks, reduced egg production and hatchability Fish: 100 (total)
Other species: 150 (total) [18]
Zinc Activates several enzymes. Component of many important metalloenzymes. Critically involved in cell replication and in the development of cartilage and bone [19]. Involved in protein synthesis, carbohydrate metabolism and many other biochemical reactions [20][21]. Retarded growth, decreased feed intake, abnormal skeletal formation, alopecia, dermatitis, abnormal wool/hair/feather growth and impaired reproduction. Fetal abnormalities. Reduced egg hatchability [19]. Parakeratosis, diarrhoea and thymic atrophy [22]. Dogs and cats: 200 (total) Salmonids and milk replacers for calves: 180 (total)
Piglets, sows, rabbits and all fish other than salmonids: 150 (total)
Other species and categories: 120 (total) [23].
1 The amount of inert iron is not to be taken into consideration for the calculation of the total iron content of the feed.
The source of the mineral is of crucial importance. In addition to differing by type, OTM and ITM also differ greatly in terms of how well they are absorbed and utilised by an animal. Traditionally, diets have been supplemented with inorganic sources of the mineral elements but these were found to be inefficiently utilised. Research further highlighted that the low pH environment of the upper gastrointestinal tract reduced the digestibility of inorganic salts by causing dissociation, thereby leaving the minerals susceptible to various nutrient and ingredient antagonisms that impaired absorption [24]. As pH increases in the small intestine, minerals such as Zn and Cu can additionally form insoluble hydroxide precipitates, rendering them unavailable for absorption [25]. Over the last number of years, organic mineral sources have increasingly been used instead of inorganic sources due to their apparent benefits—the organic counterparts are better protected from unwanted interactions in the GI tract and have enhanced bioavailability.

2. Inorganic Trace Minerals

Inorganic trace mineral (ITM) salts such as oxides, carbonates, chlorides and sulphates have been traditionally used in commercial feed formulations to meet the mineral needs of production animals in correcting and preventing trace mineral deficiencies. Although the inorganic form is perceived as being an inexpensive way to supplement the diet, recent research has shown far greater return on investment when using organic trace minerals (OTM) in place of ITM and this topic is discussed further in Section 4.
Feed-grade sources of trace minerals can differ greatly in purity. The biological availability of minerals from these sources also varies, with sulphates usually having higher relative bioavailability values than oxides [26]. Overall, the bioavailability of ITM are limited and high doses are needed to fulfil animal requirements which often results in an imbalance of nutrients and potential toxicity issues [27]. The concept of bioavailability is discussed in detail later.
Often, wide safety margins for mineral levels are permitted in feed formulation in an attempt to counteract dietary antagonists or to allow the mineral to act as a growth promoter [28][29]. Legal limitations can vary between regions with some permitting higher levels of supplementation than others [30]. When such high volumes are ingested, saturation of cellular metal binding proteins can occur, resulting in an increase in free ionised metal concentrations which can cause tissue damage. Toxic effects vary depending on the specific trace element in question, the total amount of that element in the diet, the age and condition of the animal and the presence or absence of certain other dietary components [27][30][31]. The toxic effect of a trace element can also be the cause of a secondary deficiency of another trace element.
The pathologies associated with Cu, Fe and Zn toxicity are often the result of damage to lipids in cell membranes leading to cell lysis. While pigs are highly tolerant to dietary Cu, which is often supplemented in excess as a growth promoter, sheep are far more susceptible to chronic Cu toxicity and supplementation is restricted to 15 mg kg−1 DM in the EU [32], although different breeds are thought to be more tolerant due to genetic differences [24]. Cattle were traditionally thought to be relatively tolerant to Cu accumulation, but with intensive systems for rearing now commonplace, Cu toxicity has been reported [33][34]. Furthermore, issues surround the use of sacrificial Cu in an attempt to avoid deficiencies due to high Mo levels in forages. The Mo binds to Cu in the rumen, together with S, to form thiomolybdates that render the Cu unavailable. Incidences of Cu toxicity have arisen from this management practice previously. Acute Cu toxicity in cattle can cause severe haemorrhagic gastroenteritis and congestion of the liver, kidneys and spleen, while chronic Cu toxicity can result in icterus, an enlarged spleen, and hepatic and renal necrosis [35][36][37][38].
Continuing with ruminants as an example, toxic effects in cattle and sheep associated with chronic high Fe intake include decreases in key performance indicators such as feed intake, weight gain and feed efficiency [27][39]. Enteritis, liver necrosis, icterus and haemoglobinuria have also been reported [35]. High Fe concentrations can also decrease absorption of other essential nutrients such as P, Mg, Se and Cu [40][41].
Manganese has a low potential for toxicity due to its poor intestinal absorption and efficient biliary elimination [42][43], but it can interact with several other dietary nutrients such as Zn and Fe by competing with Fe for intestinal absorption sites [44] or reducing tissue concentrations of Fe and Zn [45].
As with Fe, excess Zn can cause decreases in feed consumption, feed efficiency and weight gain. Zinc has also been shown to decrease Cu absorption and clinical manifestations in one study in sheep included inappetence, loss of condition, diarrhoea with dehydration or subcutaneous oedema, profound weakness and jaundice [46][47]. In cattle, toxicity from Zn can result in lesions of gastroenteritis, renal and liver necrosis [35].
In addition to the toxic effects in animals, another concern is the impact on plants and microorganisms [48]. In recent years, there has been increased awareness of the impact of environmental pollution from excreted minerals often caused by intensive animal feeding operations and the low retention rate of ITM [49][50][51]. Authorities have taken action and set maximum permitted levels for mineral concentrations in feed to protect the consumer, animals and the environment and continue to do so [52]. As such, it is imperative that the minerals that are supplemented are utilised in the most effective manner. Enhancing mineral utilisation is one of the most effective ways to ensure cost savings, improve animal health and reduce environmental impact.

3. Organic Trace Minerals

Several different types of OTM are commercially available, based on the type of ligand (amino acid, peptide, polysaccharide or organic acid) used to bond with the mineral. Functionality and pH stability differ between the products formed, yet all are still grouped together under the broad “OTM” term. Products such as amino acid complexes, amino acid chelates, polysaccharide complexes and proteinates have been shown to have different mineral binding properties and different pH stabilities based on their respective production processes [53]. Table 2 outlines the different classes of OTM and the further variation that exists between the Association of American Feed Control Officials (AAFCO) and the European Union (EU) definitions. Classes which are equivalent to each other have been grouped together.
Table 2. Organic trace mineral definitions comparing AAFCO and EU definitions.
  AAFCO   EU
Metal Proteinate (57.23) The product resulting from the chelation of a soluble salt with amino acids and/or partially hydrolysed protein. It must be declared as an ingredient as the specific metal proteinate, e.g., copper proteinate, zinc proteinate etc. Metal chelate of protein hydrolysates A powder with a minimum content of x% metal where x = 10% copper, iron, manganese and zinc.
Minimum of 50% copper, iron, manganese and 85% zinc chelated.
Chemical formula: M(x)1–3. nH2O, M = metal, x = anion of protein hydrolysates containing any amino acid from soya protein hydrolysate.
Metal Polysaccharide Complex (57.29) The product resulting from complexing of a soluble salt with a polysaccharide solution declared as an ingredient as the specific metal complex, e.g., copper polysaccharide complex, zinc polysaccharide complex etc.    
Metal Amino Acid Chelate (57.142) The product resulting from the reaction of a metal ion from a soluble metal salt with amino acids with a mole ratio of 1 mole of metal to 1 to 3 (preferably 2) moles of amino acids to form coordinate covalent bonds. The average weight of the hydrolysed amino acids must be approximately 150 and the resulting molecular weight of the chelate must not exceed 800. The minimum metal content must be declared. When used as a commercial feed ingredient, it must be declared as a specific metal amino acid chelate, e.g., copper amino acid chelate, zinc amino acid chelate etc. Metal chelate of amino acids hydrate Metal amino acid complex where the metal and the amino acids derived from soya protein are chelated via coordinate covalent bonds, as a powder with a minimum content of 10% copper and zinc, 9% iron and 8% manganese.
Chemical formula: M(x)1–3. nH2O, M = metal, x = anion of any amino acid from soya protein hydrolysate.
Maximum of 10% of the molecules exceeding 1500 Da.
Metal Amino Acid Complex (57:150) The product resulting from complexing a soluble metal salt with an amino acid(s). Mineral metal content must be declared. When used as a commercial feed ingredient, it must be declared as a specific metal amino acid complex, e.g., copper amino acid complex, zinc amino acid complex etc.    
Metal (specific amino acid) complex (57.151) The product resulting from complexing a soluble metal salt with a specific amino acid. Minimum metal content must be declared. When used as a commercial feed ingredient, it must be declared as a specific metal, specific amino acid complex, e.g., copper lysine, zinc methionine etc. Metal chelate of glycine hydrate (liquid)Metal chelate of glycine hydrate (solid) A liquid with a minimum content of 6% copper or 7% zinc.Chemical formula: M(x)1–3. nH2O, M = Cu or Zn, x = anion of glycine
A powder with a minimum content of 15% copper, iron, zinc and manganese and a maximum of 13% moisture for copper and 10% moisture for iron, zinc and manganese.Chemical formula: M(x)1–3. nH2O, M = metal, x = anion of glycine
There are several proposed theories for the enhanced mineral availability of chelates and complexes of minerals with organic ligands. Complexing minerals with organic components may increase the passive absorption of minerals in the intestine by reducing the interaction between the mineral and other potential chelators in the intestinal lumen and thus prevent the formation of insoluble complexes with substances such as hydroxides, carbonates, phosphates, oxalates and phytates, which would render the mineral unavailable for absorption [54][55][56].
Another proposed explanation is that complexing the mineral with an organic component may increase the water and lipid solubility of the mineral which may enhance passive absorption of the mineral. Complexing a mineral with an organic component may also result in a more favourable water–lipid partitioning coefficient that favours absorption over a wide range of pH values [57].
Absorption of OTM may also be affected by changes in molecular weight, geometry, charge density and size of the complex or chelate formed, that could result in different affinities of the mineral for binding sites. Additionally, differences in dissociation rates of the mineral from the organic group to which they are bound, and differences in mineral-chelate solubility are known to affect absorption [58]. Furthermore, the strength of the bonds between the organic ligands and the mineral on formation of a complex or chelate can prevent dissociation as it passes through the digestive system and enhance biological availability of the mineral [53].

4. Mineral Uptake Mechanisms

Most absorption of trace minerals occurs in the small intestine, primarily in the duodenum, although absorption can occur anywhere along the GI tract [59][60]. Copper and zinc can also be absorbed in the rumen [59][60][61]. In poultry, the proventriculus is also a potential site for absorption [59].
Several pathways exist for absorption of ITM and OTM. The homeostatic control of mineral uptake is covered extensively in the subsections and details a general model for absorption and resorption of inorganic minerals. With respect to organic trace elements, multiple studies have reported that organically bound trace minerals may be absorbed via amino acid or peptide transport pathways more effectively than through general mineral uptake pathways, which could explain their enhanced use [62][63][64][65][66][67]. With that in mind, several uptake mechanisms for OTM are outlined here but general homeostatic control mechanisms will also apply for their ultimate control.
The transport of amino acids into the cytoplasm occurs via functionally and biochemically distinct amino acid transport systems that have been defined on the basis of their amino acid selectivities and physico-chemical properties [68]. Each amino acid transport system adapts to the environmental conditions by choosing a coupling mode to achieve the affinity required for certain physiological conditions [69][70][71]. Amino acid transporters are categorised into at least 17 distinct classes [69]. Neutral amino acids are considered to be mainly transported by three systems: A, ASC and L [72]. Amino acids with short, polar, or linear side chains, such as L-alanine and L-serine are mainly transported by systems A and ASC. Large, branched and aromatic amino acids, such as L-tyrosine mainly enter cells via system L [73]. Species differences exist in the site of amino acid absorption and individual amino acids are not absorbed with equal efficiency—competition for transport is greater among amino acids for which a carrier has a greater affinity [74]. The transport of amino acids by intestinal enterocytes occurs by simple diffusion, facilitated diffusion (Na+-independent) and active transport (Na+-dependent) [75]. Brush border and basolateral membranes are crossed by amino acids, and di- and tripeptides by passive (facilitated or simple diffusion) or active (Na+ or H+ co- transporters) pathways [76]. Free amino acids use either passive or active transport systems, whereas di- and tripeptides use mainly active ones [76]. The relative significance of each route is highly dependent on the concentration of the substrate present [74]. Competitive inhibition from free amino acids is another factor to consider. A 2017 study, assessing the uptake of Zn provided by Zn-amino acid complexes, found a highly significant inhibitory effect on the increase in intracellular Zn levels after application of Zn-Glu, Zn-Lys and Zn-Met in the presence of Glu, Lys and Met respectively [65]. The same study noted uptake of Zn into cells was faster by the inorganic source of Zn tested (ZnCl2) compared to most of the Zn-amino acid complexes after 30 min but similar levels of absorption were observed after 120 min [65]. Other authors also found similar results where the uptake of Cu-amino acid complexes was lower compared to the free form of Cu in solution but the amino acid complex form facilitated Cu absorption in Caco-2 cells [77].
Animal diets are often supplemented with L-Met, DL-Met, or a hydroxyl analogue; DL-2-hydroxy-4-(methylthio)butanoic acid (DL-HMTBa), which is analogous to lactic acid [78]. Not only are the metabolism and use mechanisms different for these Met sources; they also differ in their absorption mechanisms [79]. For instance, as HMTBa is a precursor without an amino group, it is not absorbed by AA transporters, but rather by sodium-dependent and sodium-independent monocarboxylate transporters such as MCT1 [79][80][81]. As it is a racemic mixture with D- and L- enantiomers, differences in uptake mechanisms are not unexpected. This molecule has also been used for trace element conjugation and the complexes formed will be reliant on monocarboxylate transport pathways rather than amino or peptide transport mechanisms.
Short chain fatty acids such as acetate, propionate and butyrate were found to use a carrier mediated transport system specific for monocarboxylic acids such as MCT1 in addition to a non-electrogenic SCFA-/HCO3− antiporter [82][83][84].
Previous work on peptides supported the theory that their rate and extent of absorption is greater than that of free amino acids and that independent transport systems for peptides exist [74][85][86][87][88][89][90][91][92]. The usual routes of peptide absorption include passive transcellular diffusion, carrier mediated transport by the proton-dependent peptide transporter, PepT1 for di- and tripeptides, vesicle-mediated intracellular transport of oligopeptides (transcytosis), and paracellular transport across the intestinal epithelium [93][94]. Once the peptide-mineral complex reaches the small intestine, it can either be absorbed intact via the usual peptide absorption mechanisms, or the mineral can be dissociated from the complex and absorbed alone. As homeostasis is tightly controlled at the cellular and organismal level, the mineral is bound by a chaperone protein following dissociation to prevent subcellular damage occurring. One example is cellular Cu metabolism, which is modulated within cells by a host of cytosolic chaperones which control Cu trafficking [95]. The SLC31 (CTR) family of Cu transporters is a major gateway of Cu acquisition in eukaryotes, ranging from yeast to humans [96]. Other examples include the divalent metal transporter 1 (DMT 1), a member of the proton coupled metal ion transporter family [97]. Copper may also be sequestered within cells by metallothionein (MT) which is a Cu- and Zn-binding protein. Uptake at both adequate and suboptimal mineral levels is discussed in greater detail later.
A comprehensive review by Goff (2018) suggests that, when fed at high concentrations, many minerals can use paracellular absorption mechanisms, where the mineral diffuses across the tight junction, or solvent drag where the mineral moves with the bulk flow of water between intestinal epithelial cells to enter the blood. Minerals complexed to various dietary substances such as amino acids and peptides can also be absorbed via solvent drag, provided they are soluble in the unstirred water layer over the tight junction and generally less than 3.5 kDa in size. At lower dietary concentrations, the body primarily relies on transcellular absorption which requires transport proteins to move the mineral across the apical membrane [60].

4.1. Adequate Levels

Copper

In monogastric species, Cu is primarily absorbed across the stomach and small intestine by a transcellular process [98]. Transporters and proteins involved in the regulation of Cu in cattle have been characterised by Fry et al. [99]. Paracellular Cu absorption by diffusion is unlikely due to the potential difference across the tight junction, created by the high Na+ content of the interstitial space, being too highly positively charged. Paracellular absorption via solvent drag could be a minor contributor [60]. Cu and Zn are not free ions at the neutral pH of the intestine, but rather are often associated with low molecular weight binding ligands which enhance mucosal uptake of these trace minerals [100][101].
Cu homeostasis is regulated primarily by two transporters: the Cu transporter 1 (CTR1; also known as SLC31A1), which controls the uptake of Cu, and the Cu-extruding ATPase ATP7A, a recognised retromer cargo recognition complex [102]. Copper transporter 1 (CRT1) is the major transporter involved in cellular uptake of Cu by intestinal and other mammalian cells. Three different chaperone proteins have been identified—Cu chaperone protein (CCS) transports Cu to Cu/Zn superoxide dismutase in the cytosol, Cox17 transports Cu to proteins in the mitochondria that transfer Cu to cytochrome c oxidase in the inner mitochondrial membrane, and Atox1, which transports Cu to Cu ATPases in the trans-Golgi network [103][104]. If the body has adequate Cu stores, the enterocytes begin to produce MT which binds to Cu ions entering the cell in preference to the Atox1 chaperone. Much of the MT-bound Cu may be trapped in the enterocyte, which when it dies, is sloughed off and excreted with the faeces. High Cu status also reduces the amount of CTR1 in the apical membrane [60].

Iron

Iron in the ferric form (Fe3+) is poorly absorbed from the intestinal tract. The ferrous (Fe2+) form usually becomes bound to a chelator during digestion such as histidine, mucin, or fructose which enhances Fe absorption by solubilising the Fe ion and protecting it in the ferrous state [101][105]. Formation of Fe–amino acid complexes may allow the Fe to use amino acid transporters to move across the intestine [106]. Iron can also complex with gastric secretions allowing it to remain soluble at the more neutral pH environments of the intestine [105]. A chaperone protein, poy (rC)-binding protein-1 (rC), can be used for transport to the basolateral membrane. Divalent metal transporter 1 (DMT1) is the major transporter of Fe across the apical membrane and is specific for Fe2+. A ferrireductase (R), such as duodenal cytochrome B (DcytB), on the apical surface of enterocytes reduces Fe3+ prior to transport [107][108].
When Fe stores are adequate, the amount of DMT1 is reduced. The enterocytes produce ferritin (FRT), which binds and sequesters the bulk of the Fe2+ crossing the apical membrane. Hepcidin (HPC), a hormone produced in the liver, binds to ferroportin (FP), a basal membrane Fe transporter, blocking its ability to transport Fe out of the cell. Expression of hepcidin is regulated by liver Fe stores and can signal the small intestine to down regulate Fe absorption [60][107][109][110].

Manganese

Two Mn transport proteins have been well characterised using in vitro and rodent models: the cellular Mn importer, DMT1, and cellular Mn exporter, ferroportin 1 (FPN1) [111]. Manganese absorption does not appear to require the metal transporter DMT1 at adequate levels. Both hepatic ZIP14 and ZNT10 are necessary for effective secretion of Mn into the bile to prevent Mn accumulation by tissues [112]. In broilers, specific Mn transporter proteins exist within the duodenum and jejunum but are of limited capacity. The ileum of broilers is able to absorb Mn through a non-saturable process, suggesting that the absorption is occurring paracellularly across the tight junctions when Mn concentrations are high [60][113]. Uptake of Mn from amino acid complexes is likely not only mediated through transporters specific for ionized Mn2+, but also through cationic amino acid transporter (CAT) 1 and CAT 2 systems in addition to system b0,+ amino acid transporters [111].

Zinc

Intestinal Zn absorption occurs primarily in the small intestine by a transcellular transport process. The transporters required for Zn absorption are also present in the colon [114]. Intestinal Zn absorption is mainly mediated by the Zrt-, Irt-like protein (ZIP)4 (solute carrier (SLC)39A4), which imports ionic Zn from the lumen into enterocytes, and ZnT-1 (SLC30A1), which is a basolateral membrane protein exporting Zn on the basolateral side of enterocytes into the portal blood [115][116][117]. ZIP4 is considered to be the major intestinal Zn import transporter [103][118].
With adequate Zn levels in the body, the amount of ZIP4 in the apical membrane is downregulated and the enterocytes begin to produce high amounts of MT to bind any additional Zn2+. As with Cu, upon cellular death, Zn bound MT is excreted [101]. Because Zn and Cu are regulated by the same metalloprotein, one mineral can reduce the absorption and/or transfer of the other mineral [101]. Paracellular absorption of Zn is also known to occur with high Zn concentrations [119].

4.2. Suboptimal Levels

Copper

Brush border Cu metalloreductases (R) convert dietary Cu2+ to Cu+ and a Cu transporter protein (CTR1) facilitates diffusion of the Cu+ across the apical membrane where it becomes bound to a Cu chaperone protein (Atox1) [112][120]. Subsequently, Atox1 shuttles the Cu+ to the Golgi apparatus, where it is transferred to a Cu transport protein (ATP7A) capable of holding six Cu+ ions that is within the membrane of a Golgi transport vesicle. It has also been suggested that DMT1 acts as a minor pathway [121] and a Cu/Cl cotransport mechanism has also been proposed [122].

Iron

At suboptimal levels, the amount of DMT1 in the apical membrane is upregulated which can move Fe2+ across. Ferrireductase (R) can convert dietary Fe3+ to Fe2+ for absorption. Once Fe2+ crosses the apical membrane, it is picked up by a chaperone protein, poly (rC)-binding protein-1 (rC), for transport to the basolateral membrane. Ferroportin (FP) then pumps the Fe2+ across the basolateral membrane. Before the Fe2+ enters the interstitial fluid, it is converted to Fe3+ by Cu-hephaestin (CuHP), linked to the FP transporter [60].

Manganese

Transcellular absorption of Mn2+ involves the use of divalent metal transporters such as DMT1, ZIP8 and ZIP14 to move Mn (and other metals) across the apical membrane [60][113].

Zinc

Transcription of the Zip4 gene can increase Zn deficiency and contributes to homeostatic upregulation of Zn transport at the apical surface [112]. Other ZIP transporters have been identified (ZIP 11 and ZIP 14) that may play a minor transport role [123]. Zinc can also use DMT1 to cross the apical membrane, though it must compete for binding sites with Fe and Mn. Chaperone protein 2, in addition to 4, 5, 6 and 7, move Zn2+ to the basolateral membrane where the Zn intestinal transporter 1 (ZnT1) moves the Zn2+ into the interstitial fluid prior to it being bound to albumin [123].

References

  1. AAFCO. Feed terms and ingredient definitions. In American Association of Feed Control Officials; Eyck, R.T., Ed.; 2020 Official Publication; American Association of Feed Control Officials: Champaign, IL, USA, 2020.
  2. Hill, G.M.; Spears, J.W. Trace and Ultratrace elements in swine nutrition. In Swine Nutrition, 2nd ed.; Lewis, A.J., Southern, L.L., Eds.; CRC Press: Boca Raton, FL, USA, 2000.
  3. Turnlund, J.R. Human whole-body copper metabolism. Am. J. Clin. Nutr. 1998, 67, 960S–964S.
  4. Gaetke, L.; Chow, C. Copper toxicity, oxidative stress and antioxidant nutrients. Toxicology 2003, 189, 147–163.
  5. Crapo, J.D.; Oury, T.; Rabouille, C.; Slot, J.W.; Chang, L.Y. Copper, zinc superoxide dismutase is primarily a cytosolic protein in human cells. Proc. Natl. Acad. Sci. USA 1992, 89, 10405.
  6. Manto, M. Abnormal Copper Homeostasis: Mechanisms and Roles in Neurodegeneration. Toxics 2014, 2, 327–345.
  7. Hill, G.M. Minerals and Mineral Utilization in Swine. In Sustainable Swine Nutrition; Chiba, L.I., Ed.; Wiley-Blackwell: Chichester, UK, 2012; pp. 173–195.
  8. EFSA. Revision of the currently authorised maximum copper content in complete feed; EFSA Panel on additives products or substances used in animal feed. EFSA J. 2016, 14, 4563.
  9. Suttle, N.F. Mineral Nutrition of Livestock, 4th ed.; CABI Publishing: Wallingford, UK, 2010; pp. 1–547.
  10. Leeson, S. Copper metabolism and dietary needs. World’s Poult. Sci. J. 2009, 65, 353–366.
  11. Europe Union. Commission Implementing Regulation (EU); 2018/1039 of 23 July 2018; Publications Office of the European Union: Luxembourg, 2018; Volume 186.
  12. Rincker, M.J.; Hill, G.M.; Link, J.E.; Rowntree, J.E. Effects of dietary iron supplementation on growth performance, hematological status, and whole-body mineral concentrations of nursery pigs. J. Anim. Sci. 2004, 82, 3189–3197.
  13. Underwood, E.J. (Ed.) 2-Iron. In Trace Elements in Human and Animal Nutrition, 4th ed.; Academic Press: Cambridge, MA, USA, 1977; pp. 13–55.
  14. Europe Union. Commission Implementing Regulation (EU); 2017/2330 of 14 December 2017; Publications Office of the European Union: Luxembourg, 2017; Volume 351.
  15. Cheeke, P.R. Applied Animal Nutrition: Feeds and Feeding; Pearson: Upper Saddle River, NJ, USA, 2005.
  16. Coomer, J. The Importance of Microminerals: Manganese. Available online: https://agriking.com/the-importance-of-micro-minerals-manganese/ (accessed on 12 November 2021).
  17. Henry, P.R. 11-Manganese bioavailability. In Bioavailability of Nutrients for Animals; Ammerman, C.B., Baker, D.H., Lewis, A.J., Eds.; Academic Press: San Diego, CA, USA, 1995; pp. 239–256.
  18. Europe Union. Commission Implementing Regulation (EU); 2017/1490 of 21 August 2017; Publications office of the European Union: Luxembourg, 2017; Volume 216.
  19. Baker, D.H.; Ammerman, C.B. 17—Zinc bioavailability. In Bioavailability of Nutrients for Animals; Ammerman, C.B., Baker, D.H., Lewis, A.J., Eds.; Academic Press: San Diego, CA, USA, 1995; pp. 367–398.
  20. Hara, T.; Takeda, T.A.; Takagishi, T.; Fukue, K.; Kambe, T.; Fukada, T. Physiological roles of zinc transporters: Molecular and genetic importance in zinc homeostasis. J. Physiol. Sci. JPS 2017, 67, 283–301.
  21. Rink, L.; Gabriel, P. Zinc and the immune system. Proc. Nutr. Soc. 2000, 59, 541–552.
  22. Reese, D. Pharmacological Levels of Zinc in Nursery Diets—A Review; University of Nebraska-Lincoln: Lincoln, NE, USA, 1995.
  23. Europe Union. Commission Implementing Regulation (EU); 2016/1095 of 6 July 2016; Publications Office of the European Union: Luxembourg, 2016; Volume 182.
  24. Underwood, E.J.; Suttle, N.F. The Mineral Nutrition of Livestock; CABI Publishing: Wallingford, UK, 1999.
  25. Powell, J.J.; Whitehead, M.W.; Ainley, C.C.; Kendall, M.D.; Nicholson, J.K.; Thompson, R.P.H. Dietary minerals in the gastrointestinal tract: Hydroxypolymerisation of aluminium is regulated by luminal mucins. J. Inorg. Biochem. 1999, 75, 167–180.
  26. Pesti, G.M.; Bakalli, R.I. Studies on the feeding of cupric sulfate pentahydrate and cupric citrate to broiler chickens. Poult. Sci. 1996, 75, 1086–1091.
  27. Thompson, L.J.; Hall, J.O.; Meerdink, G.L. Toxic Effects of Trace Element Excess. Vet. Clin. N. Am. Food Anim. Pract. 1991, 7, 277–306.
  28. Flohr, J.R.; DeRouchey, J.M.; Woodworth, J.C. A survey of current feeding regimens for vitamins and trace minerals in the US swine industry. J. Swine Health Prod. 2016, 24, 290–303.
  29. Broom, L.J.; Monteiro, A.; Piñon, A. Recent Advances in Understanding the Influence of Zinc, Copper, and Manganese on the Gastrointestinal Environment of Pigs and Poultry. Animals 2021, 11, 1276.
  30. López-Alonso, M. Trace minerals and livestock: Not too much not too little. Int. Sch. Res. Not. Vet. Sci. 2012, 2012, 704825.
  31. López-Alonso, M.; Miranda, M. Implications of excessive livestock mineral supplementation on environmental pollution and human health. In Trace Elements: Environmental Sources, Geochemistry and Human Health; Nova Science: New York, NY, USA, 2012; pp. 40–53.
  32. European Commission. Commission regulation (EC) No 1334/2003 of 25 July 2003 amending the conditions for authorisation of a number of additives in feedingstuffs belonging to the group of trace elements. In Official Journal of the European Union; European Union: Geneva, Switzerland, 2003; Volume 187, p. 11.
  33. Laven, R.A.; Livesey, C.T.; Offer, N.W.; Fountain, D. Apparent subclinical hepatopathy due to excess copper intake in lactating Holstein cattle. Vet. Rec. 2004, 155, 120–121.
  34. Bidewell, C.A.; David, G.P.; Livesey, C.T. Copper toxicity in cattle. Vet. Rec. 2000, 147, 399–400.
  35. Henningson, J.N. Too Much of a Good Thing…Over Supplementation of Minerals in Cattle; Kansas State Veterinary Diagnostic Laboratory: Manhattan, KS, USA, 2016; Available online: https://www.ksvdl.org/resources/news/diagnostic_insights/january2016/over-supplementation.html (accessed on 5 December 2021).
  36. Bradley, C.H. Copper poisoning in a dairy herd fed a mineral supplement. Can. Vet. J. 1993, 34, 287–292.
  37. Minervino, A.H.H.; Barrêto Júnior, R.A.; Ferreira, R.N.F.; Rodrigues, F.A.M.L.; Headley, S.A.; Mori, C.S.; Ortolani, E.L. Clinical observations of cattle and buffalos with experimentally induced chronic copper poisoning. Res. Vet. Sci. 2009, 87, 473–478.
  38. López-Alonso, M.; Crespo, A.; Miranda, M.; Castillo, C.; Hernández, J.; Benedito, J.L. Assessment of Some Blood Parameters as Potential Markers of Hepatic Copper Accumulation in Cattle. J. Vet. Diagn. Investig. 2006, 18, 71–75.
  39. Standish, J.F.; Ammerman, C.B. Effect of Excess Dietary Iron as Ferrous Sulfate and Ferric Citrate on Tissue Mineral Composition of Sheep. J. Anim. Sci. 1971, 33, 481–484.
  40. Campbell, A.G.; Coup, M.R.; Bishop, W.H.; Wright, D.E. Effect of elevated iron intake on the copper status of grazing cattle. N. Z. J. Agric. Res. 1974, 17, 393–399.
  41. Standish, J.F.; Ammerman, C.B.; Palmer, A.Z.; Simpson, C.F. Influence of dietary iron and phosphorus on performance, tissue mineral composition and mineral absorption in steers. J. Anim. Sci. 1971, 33, 171–178.
  42. Hall, E.D.; Symonds, H.W.; Mallinson, C.B. Maximum capacity of the bovine liver to remove manganese from portal plasma and the effect of the route of entry of manganese on its rate of removal. Res. Vet. Sci. 1982, 33, 89–94.
  43. Symonds, H.W.; Hall, E.D. Acute manganese toxicity and the absorption and biliary excretion of manganese in cattle. Res. Vet. Sci. 1983, 35, 5–13.
  44. Ho, S.Y.; Miller, W.J.; Gentry, R.P.; Neathery, M.W.; Blackmon, D.M. Effects of high but nontoxic dietary manganese and iron on their metabolism by calves. J. Dairy Sci. 1984, 67, 1489–1495.
  45. Watson, L.T.; Ammerman, C.B.; Feaster, J.P.; Roessler, C.E. Influence of Manganese Intake on Metabolism of Manganese and Other Minerals in Sheep. J. Anim. Sci. 1973, 36, 131–136.
  46. Miller, W.J.; Amos, H.E.; Gentry, R.P.; Blackmon, D.M.; Durrance, R.M.; Crowe, C.T.; Fielding, A.S.; Neathery, M.W. Long-term feeding of high zinc sulfate diets to lactating and gestating dairy cows. J. Dairy Sci. 1989, 72, 1499–1508.
  47. Allen, J.G.; Masters, H.G.; Peet, R.L.; Mullins, K.R.; Lewis, R.D.; Skirrow, S.Z.; Fry, J. Zinc toxicity in ruminants. J. Comp. Pathol. 1983, 93, 363–377.
  48. Coppenet, M.; Golven, J.; Simon, J.; Le Corre, L.; Le Roy, M. Chemical evolution of soils in intensive animal-rearing farms: The example of Finistere. Agronomie 1993, 13, 77–83.
  49. Schlegel, P.; Durosoy, S.; Jongbloed, A.W. Trace Elements in Animal Production Systems; Wageningen Academic Publishers: Wageningen, The Netherlands, 2008.
  50. Bao, Y.M.; Choct, M.; Iji, P.A.; Bruerton, K. Effect of organically complexed copper, iron, manganese, and zinc on broiler performance, mineral excretion, and accumulation in tissues. J. Appl. Poult. Res. 2007, 16, 448–455.
  51. Jarosz, Ł.; Marek, A.; Grądzki, Z.; Kwiecień, M.; Kalinowski, M. The effect of feed supplementation with zinc chelate and zinc sulphate on selected humoral and cell-mediated immune parameters and cytokine concentration in broiler chickens. Res. Vet. Sci. 2017, 112, 59–65.
  52. European Commission. Commission. Commission Regulation (EC) No 1881/2006 of 19 December 2006 setting maximum levels for certain contaminants in foodstuffs. In Official Journal of the European Union; European Union: Geneva, Switzerland, 2006; Volume 364, pp. 324–365.
  53. Byrne, L.; Hynes, M.J.; Connolly, C.D.; Murphy, R.A. Influence of the chelation process on the stability of organic trace mineral supplements used in animal nutrition. Animals 2021, 11, 1730.
  54. Greene, L.W. The nutritional value of inorganic and organic mineral sources. Update of mineral nutrition of beef cattle. In Proceedings of the Plains Nutrition Council Symposium, San Antonio, TX, USA, 16–17 April 1995; pp. 23–32.
  55. Spears, J. Recent Developments in Trace Element Metabolism and Function. J. Nutr. 1989, 119, 1050.
  56. Rompala, R.E.; Halley, J.T. Explaining the absorption of chelated trace minerals: The Trojan horse of nutrition. In Feed Management; WATT Publishing: Rockford, IL, USA, 1995; Volume 46, pp. 52–58.
  57. Magee, D.F.; Dalley, A.F., II. Digestion and the Structure and Function of the Gut; Karge Continuing Education Series; Karger: Basel, Switzerland, 1986; Volume 8.
  58. Radcliffe, J.S.; Aldridge, B.E.; Saddoris, K.L. Understanding Organic Mineral Uptake Mechanisms: Experiments with Bioplex® Cu. Engormix. 2007. Available online: https://en.engormix.com/pig-industry/articles/bioplex-cu-t33770.htm (accessed on 12 November 2021).
  59. McDowell, L.R. (Ed.) Chapter 1—General Introduction. In Minerals in Animal and Human Nutrition, 2nd ed.; Elsevier: Amsterdam, The Netherlands, 2003; pp. 1–32.
  60. Goff, J.P. Invited review: Mineral absorption mechanisms, mineral interactions that affect acid-base and antioxidant status, and diet considerations to improve mineral status. J. Dairy Sci. 2018, 101, 2763–2813.
  61. López-Alonso, M.; Miranda, M. Copper Supplementation, A Challenge in Cattle. Animals 2020, 10, 1890.
  62. Muszyński, S.; Tomaszewska, E.; Kwiecień, M.; Dobrowolski, P.; Tomczyk, A. Effect of Dietary Phytase Supplementation on Bone and Hyaline Cartilage Development of Broilers Fed with Organically Complexed Copper in a Cu-Deficient Diet. Biol. Trace Elem. Res. 2018, 182, 339–353.
  63. Ashmead, H.D. Comparative intestinal absorption and subsequent metabolism of metal amino acid chelates and inorganic metal salts. In Biological Trace Element Research; Subramanian, K.S., Iyengar, G.K., Okamoto, K., Eds.; American Chemical Society: Washington, DC, USA, 1991; pp. 306–319.
  64. Aldridge, B.E.; Saddoris, K.L.; Radcliffe, J.S. Copper can be absorbed as a Cu-peptide chelate through the PepT1 transporter in the jejunum of weanling pigs. J. Anim. Sci. 2007, 85, 154–155.
  65. Sauer, A.K.; Pfaender, S.; Hagmeyer, S.; Tarana, L.; Mattes, A.-K.; Briel, F.; Küry, S.; Boeckers, T.M.; Grabrucker, A.M. Characterization of zinc amino acid complexes for zinc delivery in vitro using Caco-2 cells and enterocytes from hiPSC. Biometals 2017, 30, 643–661.
  66. Du, Z.; Hemken, R.W.; Harmon, R.J. Copper Metabolism of Holstein and Jersey Cows and Heifers Fed Diets High in Cupric Sulfate or Copper Proteinate. J. Dairy Sci. 1996, 79, 1873–1880.
  67. Glover, C.N.; Wood, C.M. Absorption of copper and copper-histidine complexes across the apical surface of freshwater rainbow trout intestine. J. Comp. Physiol. B Biochem. Syst. Environ. Physiol. 2008, 178, 101–109.
  68. Souba, W.W.; Pacitti, A.J. How amino acids get into cells: Mechanisms, models, menus, and mediators. JPEN J. Parenter. Enter. Nutr. 1992, 16, 569–578.
  69. Bröer, S. Amino Acid Transport Across Mammalian Intestinal and Renal Epithelia. Physiol. Rev. 2008, 88, 249–286.
  70. Verrey, F.; Singer, D.; Ramadan, T.; Vuille-dit-Bille, R.N.; Mariotta, L.; Camargo, S.M.R. Kidney amino acid transport. PflÜGers Arch. Eur. J. Physiol. 2009, 458, 53–60.
  71. Wong, F.H.; Chen, J.S.; Reddy, V.; Day, J.L.; Shlykov, M.A.; Wakabayashi, S.T.; Saier, M.H., Jr. The amino acid-polyamine-organocation superfamily. J. Mol. Microbiol. Biotechnol. 2012, 22, 105–113.
  72. Palacin, M.; Estevez, R.; Bertran, J.; Zorzano, A. Molecular Biology of Mammalian Plasma Membrane Amino Acid Transporters. Physiol. Rev. 1998, 78, 969–1054.
  73. Saier, M.H.; Daniels, G.A.; Boerner, P.; Lin, J. Neutral amino acid transport systems in animal cells: Potential targets of oncogene action and regulators of cellular growth. J. Membr. Biol. 1988, 104, 1–20.
  74. Webb, K.E., Jr. Intestinal absorption of protein hydrolysis products: A review. J. Anim. Sci. 1990, 68, 3011–3022.
  75. Stevens, B.R.; Kaunitz, J.D.; Wright, E.M. Intestinal transport of amino acids and sugars: Advances using membrane vesicles. Annu. Rev. Physiol. 1984, 46, 417–433.
  76. Frenhani, P.B.; Burini, R.C. Mechanisms of absorption of amino acids and oligopeptides. Control and implications in human diet therapy. Arq. Gastroenterol. 1999, 36, 227–237.
  77. Gao, S.; Yin, T.; Xu, B.; Ma, Y.; Hu, M. Amino acid facilitates absorption of copper in the Caco-2 cell culture model. Life Sci. 2014, 109, 50–56.
  78. Zhang, S.; Wong, E.A.; Gilbert, E.R. Bioavailability of different dietary supplemental methionine sources in animals. Front. Biosci. Elite 2015, 7, 478–490.
  79. Romanet, S.; Aschenbach, J.R.; Pieper, R.; Zentek, J.; Htoo, J.K.; Whelan, R.A.; Mastrototaro, L. Expression of proposed methionine transporters along the gastrointestinal tract of pigs and their regulation by dietary methionine sources. Genes Nutr. 2021, 16, 14.
  80. To, V.P.T.H.; Masagounder, K.; Loewen, M.E. Critical transporters of methionine and methionine hydroxy analogue supplements across the intestine: What we know so far and what can be learned to advance animal nutrition. Comp. Biochem. Physiol. Part A Mol. Integr. Physiol. 2021, 255, 110908.
  81. Brachet, P.; Puigserver, A. Transport of Methionine Hydroxy Analog across the Brush Border Membrane of Rat Jejunum. J. Nutr. 1987, 117, 1241–1246.
  82. Stein, J.; Zores, M.; Schröder, O. Short-chain fatty acid (SCFA) uptake into Caco-2 cells by a pH-dependent and carrier mediated transport mechanism. Eur. J. Nutr. 2000, 39, 121–125.
  83. Fafournoux, P.; Rémésy, C.; Demigné, C. Propionate transport in rat liver cells. Biochim. Biophys. Acta (BBA) Biomembr. 1985, 818, 73–80.
  84. Stumpff, F. A look at the smelly side of physiology: Transport of short chain fatty acids. PflÜGers Arch. Eur. J. Physiol. 2018, 470, 571–598.
  85. Adibi, S.A. Intestinal transport of dipeptides in man: Relative importance of hydrolysis and intact absorption. J. Clin. Investig. 1971, 50, 2266–2275.
  86. Craft, I.L.; Geddes, D.; Hyde, C.W.; Wise, I.J.; Matthews, D.M. Absorption and malabsorption of glycine and glycine peptides in man. Gut 1968, 9, 425–437.
  87. Cheng, B.; Navab, F.; Lis, M.T.; Miller, T.N.; Matthews, D.M. Mechanisms of dipeptide uptake by rat small intestine in vitro. Clin. Sci. 1971, 40, 247–259.
  88. Burston, D.; Addison, J.M.; Matthews, D.M. Uptake of dipeptides containing basic and acidic amino acids by rat small intestine in vitro. Clin. Sci. 1972, 43, 823–837.
  89. Hara, H.; Funabiki, R.; Iwata, M.; Yamazaki, K. Portal absorption of small peptides in rats under unrestrained conditions. J. Nutr. 1984, 114, 1122–1129.
  90. Silk, D.B.; Fairclough, P.D.; Clark, M.L.; Hegarty, J.E.; Marrs, T.C.; Addison, J.M.; Burston, D.; Clegg, K.M.; Matthews, D.M. Use of a peptide rather than free amino acid nitrogen source in chemically defined “elemental” diets. JPEN J. Parenter. Enter. Nutr. 1980, 4, 548–553.
  91. Asatoor, A.M.; Cheng, B.; Edwards, K.D.; Lant, A.F.; Matthews, D.M.; Milne, M.D.; Navab, F.; Richards, A.J. Intestinal absorption of dipeptides and corresponding free amino acids in Hartnup disease. Clin. Sci. 1970, 39, 1P.
  92. Hellier, M.D.; Holdsworth, C.D.; Perrett, D.; Thirumalai, C. Intestinal depeptide transport in normal and cystinuric subjects. Clin. Sci. 1972, 43, 659–668.
  93. Sun, X.; Acquah, C.; Aluko, R.E.; Udenigwe, C.C. Considering food matrix and gastrointestinal effects in enhancing bioactive peptide absorption and bioavailability. J. Funct. Foods 2020, 64, 103680.
  94. Wada, Y.; Lonnerdal, B. Bioactive peptides derived from human milk proteins—Mechanisms of action. J. Nutr. Biochem. 2013, 25, 503–514.
  95. Doguer, C.; Ha, J.-H.; Collins, J.F. Intersection of Iron and Copper Metabolism in the Mammalian Intestine and Liver. Compr. Physiol. 2018, 8, 1433–1461.
  96. Kim, H.; Wu, X.; Lee, J. SLC31 (CTR) family of copper transporters in health and disease. Mol. Asp. Med. 2013, 34, 561–570.
  97. Puchkova, L.V.; Broggini, M.; Polishchuk, E.V.; Ilyechova, E.Y.; Polishchuk, R.S. Silver Ions as a Tool for Understanding Different Aspects of Copper Metabolism. Nutrients 2019, 11, 1364.
  98. Van den Berghe, P.; Klomp, L. New Developments in the regulation of intestinal copper absorption. Nutr. Rev. 2009, 67, 658–672.
  99. Fry, R.S.; Spears, J.W.; Lloyd, K.E.; O’Nan, A.T.; Ashwell, M.S. Effect of dietary copper and breed on gene products involved in copper acquisition, distribution, and use in Angus and Simmental cows and fetuses. J. Anim. Sci. 2013, 91, 861–871.
  100. Hambidge, K.M.; Casey, C.E.; Krebs, N.F. 1-Zinc. In Trace Elements in Human and Animal Nutrition, 5th ed.; Mertz, W., Ed.; Academic Press: San Diego, CA, USA, 1986; pp. 1–137.
  101. O’Dell, B.L.; Sunde, R.A. Handbook of Nutritionally Essential Mineral Elements; CRC Press: New York, NY, USA, 1997.
  102. Curnock, R.; Cullen, P.J. Mammalian copper homeostasis requires retromer-dependent recycling of the high-affinity copper transporter 1. J. Cell Sci. 2020, 133, jcs249201.
  103. Spears, J.W. Advancements in Ruminant Trace Mineral Nutrition. In Proceedings of the Cornell Nutrition Conference for Feed Manufacturers, New York, NY, USA, 22–24 October 2013.
  104. Kim, B.E.; Nevitt, T.; Thiele, D.J. Mechanisms for copper acquisition, distribution and regulation. Nat. Chem. Biol. 2008, 4, 176–185.
  105. Conrad, M.E.; Umbreit, J.N. Pathways of iron absorption. Blood Cells Mol. Dis. 2002, 29, 336–355.
  106. Mackenzie, B.; Garrick, M.D. Iron Imports. II. Iron uptake at the apical membrane in the intestine. Am. J. Physiol. Gastrointest. Liver Physiol. 2005, 289, G981–G986.
  107. De Domenico, I.; McVey Ward, D.; Kaplan, J. Regulation of iron acquisition and storage: Consequences for iron-linked disorders. Nat. Rev. Mol. Cell Biol. 2008, 9, 72–81.
  108. Duck, K.A.; Connor, J.R. Iron uptake and transport across physiological barriers. Biometals 2016, 29, 573–591.
  109. Gozzelino, R.; Arosio, P. Iron Homeostasis in Health and Disease. Int. J. Mol. Sci. 2016, 17, 130.
  110. Sangkhae, V.; Nemeth, E. Regulation of the Iron Homeostatic Hormone Hepcidin. Adv. Nutr. 2017, 8, 126–136.
  111. Bai, S.; Zhang, K.; Ding, X.; Wang, J.; Zeng, Q.; Peng, H.; Bai, J.; Xuan, Y.; Su, Z.; Wu, B. Uptake of Manganese from the Manganese-Lysine Complex in Primary Chicken Intestinal Epithelial Cells. Animals 2019, 9, 559.
  112. Cousins, R.J.; Liuzzi, J.P. Chapter 61—Trace Metal Absorption and Transport. In Physiology of the Gastrointestinal Tract, 6th ed.; Said, H.M., Ed.; Academic Press: Cambridge, MA, USA, 2018; pp. 1485–1498.
  113. Jenkitkasemwong, S.; Wang, C.-Y.; Mackenzie, B.; Knutson, M.D. Physiologic implications of metal-ion transport by ZIP14 and ZIP8. Biometals 2012, 25, 643–655.
  114. Gopalsamy, G.; Alpers, D.; Binder, H.; Tran, C.; Ramakrishna, B.; Brown, I.; Manary, M.; Mortimer, E.; Young, G. The Relevance of the Colon to Zinc Nutrition. Nutrients 2015, 7, 572.
  115. Cousins, R.J.; Liuzzi, J.P.; Lichten, L.A. Mammalian Zinc Transport, Trafficking, and Signals. J. Biol. Chem. 2006, 281, 24085–24089.
  116. Maares, M.; Haase, H. A Guide to Human Zinc Absorption: General Overview and Recent Advances of In Vitro Intestinal Models. Nutrients 2020, 12, 762.
  117. Eide, D.J. Zinc transporters and the cellular trafficking of zinc. Biochim. Biophys. Acta (BBA)-Mol. Cell Res. 2006, 1763, 711–722.
  118. Yuzbasiyan-Gurkan, V.; Bartlett, E. Identification of a unique splice site variant in SLC39A4 in bovine hereditary zinc deficiency, lethal trait A46: An animal model of acrodermatitis enteropathica. Genomics 2006, 88, 521–526.
  119. Condomina, J.; Zornoza-Sabina, T.; Granero, L.; Polache, A. Kinetics of zinc transport in vitro in rat small intestine and colon: Interaction with copper. Eur. J. Pharm. Sci. 2002, 16, 289–295.
  120. Hashimoto, A.; Kambe, T. Mg, Zn and Cu Transport Proteins: A Brief Overview from Physiological and Molecular Perspectives. J. Nutr. Sci. Vitaminol. 2015, 61, S116–S118.
  121. Lutsenko, S.; Barnes, N.L.; Bartee, M.Y.; Dmitriev, O.Y. Function and Regulation of Human Copper-Transporting ATPases. Physiol. Rev. 2007, 87, 1011–1046.
  122. Zimnicka, A.M.; Ivy, K.; Kaplan, J.H. Acquisition of dietary copper: A role for anion transporters in intestinal apical copper uptake. Am. J. Physiol. Cell Physiol. 2011, 300, C588–C599.
  123. Cousins, R.J. Gastrointestinal factors influencing zinc absorption and homeostasis. Int. J. Vitam. Nutr. Res. 2010, 80, 243–248.
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