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Zinc

Zn

Zinc, Zn - Essential Metal

Zn

Daily Requirement:

Modified DV:

RDA ?:

Adequate Intake ?:

9.4

true

mg/day

mg/day

Min Deficiency:

Max Toxicity:

Tolerable UL

Animal:Plant Conv:

40

mg/day

mg/day

mg/day

Date Discovered:

1746

Short Description:

Animal products such as meat, fish, shellfish, fowl, eggs, and dairy contain zinc. The concentration of zinc in plants varies with the level in the soil. With adequate zinc in the soil, the food plants that contain the most zinc are wheat (germ and bran) and various seeds, including sesame, poppy, alfalfa, celery, and mustard. Zinc is also found in beans, nuts, almonds, whole grains, pumpkin seeds, sunflower seeds, and blackcurrant.

Interpretation:

Zinc

• Why is Zn important in biology

Zinc fingers, transcription factors use zinc for DNA binding,

• What are the general function s of ZnT and ZIP proteins

ZnT zn efflux out of the cells, ZIP - import -

• What is the ZIP protein that imports Zn into enterocytes, what turns this gene on/off

ZIP4

• Is Zn deficiency a problem

It can be, in vegetarian diets, and elderly.

• How is Zn deficiency related to cancer risk

cell models, animal models, Zn def increase DNA mutations, inhibits binding of p53 DNA

• What populations could benefit from Zn supplements in terms of immune function

Zn supplements in elderly might help immune function, reduction in infections.

History & Discovery:

Zinc is an essential trace element for humans, animals, plants and for microorganisms and is necessary for prenatal and postnatal development. It is the second most abundant trace metal in humans after iron and it is the only metal which appears in all enzyme classes.

  • The number of genes coding for proteins with zinc-binding domains is conservatively estimated at >3% of the human genome but possibly is as much as 10%

  • Zinc is a component of >1,000 proteins including DNA-binding proteins with zinc fingers, copper/zinc superoxide dismutase (SOD), and several proteins involved in DNA-damage repair such as p53, which is mutated in half of human tumors

  • Animals regulate zinc gain and loss efficiently. In humans, about 1% of the total body zinc content is replenished daily by the diet

  • In mammals, inadequate levels of zinc in the diet lead to dermatologic lesions, growth retardation, mental disorders, and compromised function of the immune and reproductive systems

  • High levels of zinc can be cytotoxic. Thus, cells must maintain tight control over intracellular zinc levels. This control is achieved through a balance of zinc efflux, cellular zinc storage, and zinc uptake


Digestion:

Foods rich in zinc include red meat and seafood. Several plant sources, such as whole grains and legumes, also contain zinc, but the zinc in these sources are much less bioavailable.


Phytate, which is found at high levels in cereal grains and legumes, forms a tight complex with zinc (or iron) and decreases its absorption

Absorption and Storage:

Important Pathways:

Zinc Transport Proteins


  • The first mammalian zinc transporter gene, ZnT1, was identified in 1995

  • Two protein families have now been implicated in zinc transport

  • The ZnT proteins lower intracellular zinc by mediating zinc efflux from cells or influx into intracellular vesicles

  • The Zip (Zrt- and Irt-like proteins) proteins promote zinc transport from the extracellular fluid or from intracellular vesicles into the cytoplasm

  • The mammalian Zip family consists of 14 members

  • Zip proteins are responsible for transporting zinc into cells

  • Zip 4 is thought to be primary dietary zinc importing protein of intestinal enterocytes



Deficiency Diseases, Detection, Cures:

Zinc Deficiency


  • A significant portion of the North American population does not get adequate zinc

  • 10% of the U.S. population consumes less than half RDA for zinc, especially those who consume little meat and/or consume high phytate-containing food sources

  • Nearly two billion people in the developing world are deficient in zinc. Groups at risk include children in developing countries and elderly with chronic illnesses

  • Foods rich in zinc include red meat and seafood. Several plant sources, such as whole grains and legumes, also contain zinc, but the zinc in these sources are much less bioavailable.

  • Phytate, which is found at high levels in cereal grains and legumes, forms a tight complex with zinc (or iron) and decreases its absorption

  • Dietary Reference Intakes for zinc suggest that, because of lower absorption of zinc, those consuming vegetarian diets, especially with phytate-zinc molar ratios > 15, may require as much as 50% more zinc than non-vegetarians


Zinc deficiency and its relevance to cancer


  • The link between zinc deficiency and cancer has been established in human, animal and cell culture studies

  • Zinc deficiency causes oxidative DNA damage and chromosome breaks have been reported in animals fed a zinc-deficient diet

  • In rats, dietary zinc deficiency causes an increased susceptibility to tumor development when exposed to carcinogenic compounds

  • Cell culture studies have also shown that zinc deficiency can lead to increased oxidative damage

  • Zinc supplementation strategies may not only aid in the prevention of cancer, but could also play an important role in limiting its malignancy. Zinc plays an important role in protecting DNA from damage as an antioxidant and a component of many DNA repair proteins

  • Over 50% of human malignancies contain a mutation in p53

  • The majority of these mutations are found in the region of the gene that encodes for the DNA-binding region of p53

  • This binding region contains zinc, and to coordinate the events related to DNA repair, p53 must be able to bind to specific DNA-binding domains to transcriptionally activate downstream targets involved in DNA repair

Zinc, Immune Function and the Elderly

  • Zinc deficiency has been suggested to be a risk factor for immune deficiency and subsequent infection relapses in the elderly

  • Zinc is essential to the function of all highly proliferating cells in the human body, especially the immune system

  • Zinc is crucial to the normal development of immune cells, and it plays an important role in maintaining the activity of a range of immune cells, including neutrophils, monocytes, macrophages, natural killer cells, and B and T cells

  • Thymus atrophy, lymphopenia, and other defects in T cell function have been observed in both zinc deficiency and in the elderly

  • Therefore, zinc-deficient subjects have a greater susceptibility to a variety of pathogens

  • Low zinc consumption has been reported in the elderly. One study estimated that zinc ingestion was below the RDA in >90% of people aged 60–89

Effect of Zn Supplementation on Immune Function

  • Elderly (>65), zinc deficient subjects were randomly assigned to zincsupplementation or the placebo group for 1 year

  • Each day for 12 mo, subjects in the zinc-supplemented group received 1 capsule of zinc gluconate (15 mg elemental zinc) orally 1 h before breakfast and 2 capsules before going to bed


The 4 treatment groups:

  1. 8000 mg of ascorbic acid (to be divided over 2-3 times per day with meals),

  2. 50 mg of zinc gluconate at bedtime,

  3. both therapies,

  4. usual care without any study medications.


Genetic Diseases:

References:

Gastric and Colonic Zinc Transporter ZIP11 (Slc39a11) in Mice Responds to Dietary Zinc and Exhibits Nuclear Localization

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3827636/


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