Zinc in biology

Zinc is an essential trace element for humans[1][2][3] and other animals,[4] for plants[5] and for microorganisms.[6] Zinc is required for the function of over 300 enzymes and 1000 transcription factors,[3] and is stored and transferred in metallothioneins.[7][8] It is the second most abundant trace metal in humans after iron and it is the only metal which appears in all enzyme classes.[5][3]

In proteins, zinc ions are often coordinated to the amino acid side chains of aspartic acid, glutamic acid, cysteine and histidine. The theoretical and computational description of this zinc binding in proteins (as well as that of other transition metals) is difficult.[9]

Roughly 2–4 grams of zinc[10] are distributed throughout the human body. Most zinc is in the brain, muscle, bones, kidney, and liver, with the highest concentrations in the prostate and parts of the eye.[11] Semen is particularly rich in zinc, a key factor in prostate gland function and reproductive organ growth.[12]

Zinc homeostasis of the body is mainly controlled by the intestine. Here, ZIP4 and especially TRPM7 were linked to intestinal zinc uptake essential for postnatal survival.[13][14]

In humans, the biological roles of zinc are ubiquitous.[15][2] It interacts with "a wide range of organic ligands",[15] and has roles in the metabolism of RNA and DNA, signal transduction, and gene expression. It also regulates apoptosis. A review from 2015 indicated that about 10% of human proteins (~3000) bind zinc,[16] in addition to hundreds more that transport and traffic zinc; a similar in silico study in the plant Arabidopsis thaliana found 2367 zinc-related proteins.[5]

In the brain, zinc is stored in specific synaptic vesicles by glutamatergic neurons and can modulate neuronal excitability.[2][3][17] It plays a key role in synaptic plasticity and so in learning.[2][18] Zinc homeostasis also plays a critical role in the functional regulation of the central nervous system.[2][17][3] Dysregulation of zinc homeostasis in the central nervous system that results in excessive synaptic zinc concentrations is believed to induce neurotoxicity through mitochondrial oxidative stress (e.g., by disrupting certain enzymes involved in the electron transport chain, including complex I, complex III, and α-ketoglutarate dehydrogenase), the dysregulation of calcium homeostasis, glutamatergic neuronal excitotoxicity, and interference with intraneuronal signal transduction.[2][19] L- and D-histidine facilitate brain zinc uptake.[20] SLC30A3 is the primary zinc transporter involved in cerebral zinc homeostasis.[2]

  1. ^ Maret W (2013). "Zinc and Human Disease". In Sigel A, Sigel H, Freisinger E, Sigel RK (eds.). Interrelations between Essential Metal Ions and Human Diseases. Metal Ions in Life Sciences. Vol. 13. Springer. pp. 389–414. doi:10.1007/978-94-007-7500-8_12. ISBN 978-94-007-7499-5. PMID 24470098.
  2. ^ a b c d e f g Prakash A, Bharti K, Majeed AB (April 2015). "Zinc: indications in brain disorders". Fundamental & Clinical Pharmacology. 29 (2): 131–149. doi:10.1111/fcp.12110. PMID 25659970. S2CID 21141511.
  3. ^ a b c d e Cherasse Y, Urade Y (November 2017). "Dietary Zinc Acts as a Sleep Modulator". International Journal of Molecular Sciences. 18 (11): 2334. doi:10.3390/ijms18112334. PMC 5713303. PMID 29113075. Zinc is the second most abundant trace metal in the human body, and is essential for many biological processes.  ... The trace metal zinc is an essential cofactor for more than 300 enzymes and 1000 transcription factors [16]. ... In the central nervous system, zinc is the second most abundant trace metal and is involved in many processes. In addition to its role in enzymatic activity, it also plays a major role in cell signaling and modulation of neuronal activity.
  4. ^ Prasad AS (2008). "Zinc in human health: effect of zinc on immune cells". Molecular Medicine. 14 (5–6): 353–357. doi:10.2119/2008-00033.Prasad. PMC 2277319. PMID 18385818.
  5. ^ a b c Broadley MR, White PJ, Hammond JP, Zelko I, Lux A (2007). "Zinc in plants". The New Phytologist. 173 (4): 677–702. Bibcode:2007NewPh.173..677B. doi:10.1111/j.1469-8137.2007.01996.x. PMID 17286818.
  6. ^ Zinc's role in microorganisms is particularly reviewed in: Sugarman B (1983). "Zinc and infection". Reviews of Infectious Diseases. 5 (1): 137–147. doi:10.1093/clinids/5.1.137. PMID 6338570.
  7. ^ Cotton et al. 1999, pp. 625–629
  8. ^ Plum LM, Rink L, Haase H (April 2010). "The essential toxin: impact of zinc on human health". International Journal of Environmental Research and Public Health. 7 (4): 1342–1365. doi:10.3390/ijerph7041342. PMC 2872358. PMID 20617034.
  9. ^ Brandt EG, Hellgren M, Brinck T, Bergman T, Edholm O (February 2009). "Molecular dynamics study of zinc binding to cysteines in a peptide mimic of the alcohol dehydrogenase structural zinc site". Physical Chemistry Chemical Physics. 11 (6): 975–983. Bibcode:2009PCCP...11..975B. doi:10.1039/b815482a. PMID 19177216. Archived from the original on 2021-05-18. Retrieved 2022-07-02.
  10. ^ Rink L, Gabriel P (November 2000). "Zinc and the immune system". The Proceedings of the Nutrition Society. 59 (4): 541–552. doi:10.1017/S0029665100000781. PMID 11115789.
  11. ^ Wapnir RA (1990). Protein Nutrition and Mineral Absorption. Boca Raton, Florida: CRC Press. ISBN 978-0-8493-5227-0. Archived from the original on 2022-04-25. Retrieved 2022-07-02.
  12. ^ Berdanier CD, Dwyer JT, Feldman EB (2007). Handbook of Nutrition and Food. Boca Raton, Florida: CRC Press. ISBN 978-0-8493-9218-4. Archived from the original on 2021-04-13. Retrieved 2022-07-02.
  13. ^ Mittermeier L, Demirkhanyan L, Stadlbauer B, Breit A, Recordati C, Hilgendorff A, et al. (March 2019). "TRPM7 is the central gatekeeper of intestinal mineral absorption essential for postnatal survival". Proceedings of the National Academy of Sciences of the United States of America. 116 (10): 4706–4715. Bibcode:2019PNAS..116.4706M. doi:10.1073/pnas.1810633116. PMC 6410795. PMID 30770447.
  14. ^ Kasana S, Din J, Maret W (January 2015). "Genetic causes and gene–nutrient interactions in mammalian zinc deficiencies: acrodermatitis enteropathica and transient neonatal zinc deficiency as examples". Journal of Trace Elements in Medicine and Biology. 29: 47–62. Bibcode:2015JTEMB..29...47K. doi:10.1016/j.jtemb.2014.10.003. PMID 25468189.
  15. ^ a b Hambidge KM, Krebs NF (April 2007). "Zinc deficiency: a special challenge". The Journal of Nutrition. 137 (4): 1101–1105. doi:10.1093/jn/137.4.1101. PMID 17374687.
  16. ^ Djoko KY, Ong CL, Walker MJ, McEwan AG (July 2015). "The Role of Copper and Zinc Toxicity in Innate Immune Defense against Bacterial Pathogens". The Journal of Biological Chemistry. 290 (31): 18954–18961. doi:10.1074/jbc.R115.647099. PMC 4521016. PMID 26055706. Zn is present in up to 10% of proteins in the human proteome and computational analysis predicted that ~30% of these ~3000 Zn-containing proteins are crucial cellular enzymes, such as hydrolases, ligases, transferases, oxidoreductases, and isomerases (42,43).
  17. ^ a b Bitanihirwe BK, Cunningham MG (November 2009). "Zinc: the brain's dark horse". Synapse. 63 (11): 1029–1049. doi:10.1002/syn.20683. PMID 19623531. S2CID 206520330.
  18. ^ Nakashima AS, Dyck RH (March 2009). "Zinc and cortical plasticity". Brain Research Reviews. 59 (2): 347–373. doi:10.1016/j.brainresrev.2008.10.003. PMID 19026685. S2CID 22507338.
  19. ^ Tyszka-Czochara M, Grzywacz A, Gdula-Argasińska J, Librowski T, Wiliński B, Opoka W (May 2014). "The role of zinc in the pathogenesis and treatment of central nervous system (CNS) diseases. Implications of zinc homeostasis for proper CNS function" (PDF). Acta Poloniae Pharmaceutica. 71 (3): 369–377. PMID 25265815. Archived (PDF) from the original on August 29, 2017.
  20. ^ Yokel RA (November 2006). "Blood-brain barrier flux of aluminum, manganese, iron and other metals suspected to contribute to metal-induced neurodegeneration". Journal of Alzheimer's Disease. 10 (2–3): 223–253. doi:10.3233/JAD-2006-102-309. PMID 17119290.
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