Zinc Nutrition – Zinc is component of more than 300 enzymes & important in immunity regulation
In 1869 Raulin was the first to describe the need of zinc in biological systems, namely in studying the growth of Aspergillus niger. The essentiality of zinc for animals was described for the first time several decades later in 1934 by Todd and his group.
It was not until the 1960s that zinc deficiency was observed in humans by Ananda Prasad. He described a zinc deficiency syndrome in Iranian and Egyptian subjects who were extremely susceptible to bacterial, fungal, and parasitic infections.
Zinc has been found in every tissue in the animal body. The element tends to accumulate in the bones rather than the liver, which is the main storage organ of many of the other trace elements. High concentrations have been found in the skin, hair and wool of animals. Several enzymes (more than 300 enzymes) in the animal body are known to contain zinc; these enzymes include carbonic anhydrase, pancreatic carboxypeptidase, lactate dehydrogenase, alcohol dehydrogenase, alkaline phosphatase and thymidine kinase. In addition, zinc is an activator of several enzyme systems. It is involved in cell replication and differentiation, particularly in nucleic acid metabolism. Among the other physiological functions of zinc are the production, storage and secretion of hormones, involvement in the immune system and electrolyte balance.
Gross signs of zinc deficiency in chicks are retarded growth, foot abnormalities, ‘frizzled’ feathers, parakeratosis and a bone abnormality referred to as ‘swollen hock syndrome’. Symptoms of zinc deficiency in calves include inflammation of the nose and mouth, stiffness of the joints, swollen feet and parakeratosis. The response of severely zinc-deficient calves to supplemental zinc is rapid and dramatic. Improvements in skin condition are usually noted within 2–3 days.
Manifestations of zinc deficiency, responsive to zinc therapy, have been observed in growing and mature cattle in parts of Guyana, Greece, Australia and Scandinavia. As levels in the pasture herbage are apparently comparable with those of other areas, the deficiency is believed to be conditioned by some factor in the herbage or general environment. In dairy cows, low dietary zinc concentrations are associated with high somatic cell counts in their milk.
Zinc does not donate or accept electrons, and therefore zinc is not involved in oxidation–reduction reactions. However, Zn2+ has strong attraction to electron pairs. In the plasma and intracellular fluid, free zinc reacts rapidly with water to yield an insoluble zinc hydroxide: Zn2+ + H2O → Zn(OH)2↓ + 2H+
Therefore, proteins are required to transport Zn in animals. In animals, the whole-body content of zinc ranks second among trace minerals behind iron (i.e., 2–2.5 g of zinc/70 kg BW), with most of zinc being present in skeletal muscle (47%), bone (29%), skin (6%), liver (5%), brain (1.5%), kidneys (0.7%), and heart (0.4%). Zinc is rich in the seminal fluid of males. In all cells, zinc exists primarily as a complex with proteins and nucleic acids.
In gastric fluid with an acidic environment, zinc can exist as a free ion. In the lumen of the small intestine with an alkaline solution, zinc binds to gastroferrin to increase its solubility. Zinc is absorbed into the enterocyte via the apical membrane transporters: ZIP4 (a member of the zinc family of transporters) and DCT-1. Expression of ZIP4 is stimulated by dietary zinc intake.
Upon entering the enterocyte, zinc binds primarily to a cytosolic protein called cysteine-rich intracellular protein and possibly a nonspecific binding protein (NSBP) for transport to the basolateral membrane. This mineral may also bind to cytosolic metallothionein for temporary storage in enterocytes. Zinc exits the enterocyte across its basolateral membrane into the lamina propria via Zn transporter-1, then enters the portal circulation. Intestinal absorption of zinc is reduced by various minerals (e.g., calcium and copper) and phytate.
Absorbed zinc enters the portal circulation. In the plasma, 60% and 30% of the zinc binds to albumin and α2-macroglobulin, respectively, and about 10% of the zinc binds to other serum factors. Free Zn is present in serum at about 0.1 µM. Zinc in the blood is taken up by the liver via ZIP2/3, and exits this organ via ZnT-1 into the systemic circulation. Various other organs take up zinc via ZIPs (e.g., kidneys, ZIP4; pancreas, ZIP1; spleen and bone marrow, ZIP2/3). There is evidence that voltage-gated Ca2+ channels take part in the transport of Zn2+ into animal cells. Once entering the cells, zinc is assimilated into various metalloproteins, including metallothionein. Metallothionein is a small protein (MW, 10,000), and about 1/3 of its AA residues are cysteine. Metallothionein may act as a reservoir for zinc, and as a detoxifying agent for toxic heavy metals, such as cadmium.
Zinc-Dependent Enzymes and Binding Proteins in Animals
| Enzyme | Function |
| Alanyl-glycine dipeptidase | Hydrolysis of alanyl-glycine dipeptide |
| Alcohol dehydrogenase | Alcohol catabolism |
| Alkaline phosphatase | Hydrolyzes phosphate monoesters |
| Aminolevulinic acid dehydrogenase | Biosynthesis of heme |
| Aminopeptidase (Zn2+, Co2+, Mo2+) | Hydrolysis of polypeptides |
| Angiotensin-converting enzyme | Regulation of Na balance and blood pressure |
| Carbonic anhydrase | CO2 + H2O → H2CO3 ↔ H+ + HCO3- |
| Carboxypeptidase A | Digestion of dietary protein |
| Carboxypeptidase B | Digestion of dietary protein |
| Carnosidase (Zn2+, Mn2+) | Carnosine + H2O → l-Histidine + β-Alanine |
| Component 9 of complement | Immune system |
| Dehydroquinate synthase | Microbial synthesis of aromatic amino acids |
| DNAase | DNA degradation |
| DNA polymerase | DNA synthesis from deoxyribonucleotides |
| Enolase (Zn2+, Mg2+, Mn2+) | 2-Phospho-d-glycerate ↔ Phosphoenolpyruvate + H2O |
| Fructose-1,6-bisphosphatase | Gluconeogenesis |
| Galactosyltransferase complex | Synthesis of lactose |
| Glutamate dehydrogenase | Glutamate + NAD+ ↔ NH4+ + α-Ketoglutarate + NADH + H+ |
| Glycyl-glycine dipeptidase | Hydrolysis of glycyl-glycine |
| Glycyl-leucine dipeptidase (Zn2+, Mn2+) | Hydrolysis of glycyl-leucine |
| Glyoxalase | Detoxication of aldehydes |
| Insulin in secretory vesicles | Used in stabilizing insulin |
| Lactate dehydrogenase | Pyruvate ↔ Lactate |
| Mannosidase | Hydrolysis of mannose |
| Metallothionein | Storage or detoxication of zinc |
| 5′-Nucleotidase | Cleavage of phosphate from nucleoside 5′-monophosphates |
| aPoly(ADP-ribose)polymerase | Repairs DNA damage |
| Protein kinase C | Cell signal transduction |
| Phospholipase C | PIP2 → 1,2-Diacylglycerol + IP3 |
| aRetinoic acid receptor | DNA binding and genetic regulation |
| RNAase | RNA degradation |
| RNA polymerase | RNA synthesis from ribonucleotides |
| aSteroid hormone receptor | DNA binding and genetic regulation |
| Superoxide dismutase (cytosol) | Removal O2– |
| Thymulin | Hormone of the immune system |
| aTranscription factors | Regulation of synthesis of many mRNAs |
| Triosephosphate isomerase | Dihydroxyacetone-P ↔ d-Glyceraldehyde 3-P |
| Tripeptidase (Zn2+ or Co2+) | Hydrolysis of tripeptides |
| PIP2, phosphatidylinositol 4,5-bisphosphate; IP3, inositol 1,4,5-trisphosphate. a Indicates the presence of zinc finger structure. |
There are about 100 zinc enzymes associated with the mammalian genome. Examples of the zinc-dependent enzymes and zinc-binding proteins are summarized in Table. To maintain a zinc finger structure (a structural configuration that contains zinc ions to stabilize a polypeptide molecule) in proteins, zinc stabilizes the macromolecules (e.g., insulin and nucleic acids) and regulates gene expression in cells. Thus, zinc plays a signicant role in genomic stability; the metabolism of protein (both protein synthesis and degradation), nucleic acids, carbohydrate, lipids, and energy; integrity and function of cells (including epithelial cells); transport of vitamins A and E in the blood; immune response; and reproduction (e.g., male and female fertility); and collagen and keratin formation, as well as healthy development and repair of hair, skin and nails.
Furthermore, high dietary zinc (e.g., 2425–3000 ppm ZnO) can reduce the number of bacteria (e.g., Enterobacteriaceae, the Escherichia group, and Lactobacillus spp.) in the stomach, small intestine, and large intestine of weaned piglets. The inclusion of 0.3% ZnO (3000 ppm) in diets can prevent diarrhoea, while enhancing the growth and feed efficiency.
