nutrition

Zinc functions of R.Borgacci

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What is zinc?

Zinc, which is considered an essential nutrient for human health, performs numerous functions throughout the body.

Zinc in the human body

The human body contains about 2-4 grams of zinc. Most of it is in the organs, with greater concentrations in the prostate and in the eyes; it is also abundant in the brain, muscles, bones, kidneys and liver. Sperm is particularly rich in zinc, a key factor in the functioning of the prostate gland and the growth of reproductive organs.

Functions and Biological Role

Zinc seems to have very important biological functions and roles, especially in the constitution and functioning of enzymes, nucleic acids and proteins of various kinds. Within peptides, zinc ions are often coordinated to the side chains of amino acids of aspartic acid, glutamic acid, cysteine ​​and histidine. However, the theoretical and computational description of this bond of zinc in proteins - as well as that of other transition metals - is difficult to explain.

In humans, the biological functions and roles of zinc are ubiquitous. It interacts with a wide range of organic ligands and has essential functions in the metabolism of RNA and DNA nucleic acids, in signal transduction and in gene expression. Zinc also regulates apoptosis - cell death. A 2006 study has estimated that about 10% of human proteins are linked to the biological role of zinc, not to mention the hundreds of other peptide factors involved in mineral transport; a similar "in silico" study - computer simulation - in the Arabidopsis thaliana plant found 2367 zinc-bound proteins.

In the brain, zinc is stored in specific synaptic vesicles of glutamatergic neurons and can modulate neuronal excitability. It plays a key role in synaptic plasticity and therefore in the complex learning function. Zinc homeostasis also plays a critical role in the functional regulation of the central nervous system. It is believed that imbalances in zinc homeostasis in the central nervous system may cause excessive concentrations of synaptic zinc with potential:

  • Neurotoxicity, due to mitochondrial oxidative stress - for example, interrupting certain enzymes involved in the electron transport chain, such as complex I, complex III and α-ketoglutarate dehydrogenase
  • Unevenness of calcium homeostasis
  • Glutammatergic neuronal excitotoxicity
  • Interference with intraneuronal signal transduction.

L- and D-histidine - isomers of the same amino acid - facilitate zinc absorption in the brain. SLC30A3 - solute carrier family 30 member 3 or zinc transporter 3 - is the main zinc carrier involved in brain mineral homeostasis.

Enzymes

Among the many functions and bio-chemical roles of zinc, we have said, there is that of the constitution of enzymes.

Zinc (more precisely the Zn2 + ion) is a very efficient Lewis acid, a property that makes it a catalytic agent useful for hydroxylation and other enzymatic reactions. It also has a flexible coordination geometry, which allows the proteins that use it to quickly change conformation to perform various biological reactions. Two examples of zinc-containing enzymes are: carbonic anhydrase and carboxypeptidase, necessary for the processes of carbon dioxide (CO2) regulation and digestion of proteins.

Zinc and carbonic anhydrase

In the blood of vertebrates, the enzyme carbonic anhydrase converts CO2 into bicarbonate and the same enzyme transforms bicarbonate into CO2 subsequently exhaled through the lungs. Without this enzyme, at normal blood pH, the conversion would occur about a million times slower, or would require a pH of 10 or more. Unrelated β-carbonic anhydrase is indispensable for plants due to the formation of leaves, the synthesis of acetic indole acid (auxin) and alcoholic fermentation.

Zinc and carboxypeptidase

The carboxypeptidase enzyme breaks down peptide bonds during protein digestion; more precisely, it facilitates nucleophilic attack on the CO group of the peptide, generating a highly reactive nucleophile or activating the carbonyl for attack

by polarization. It also stabilizes the tetrahedral intermediate - or transition state - which

it is generated with the nucleophilic attack on the carbonyl carbon. Finally it must stabilize the atom of

amide nitrogen so as to make it an appropriate outgoing group, once the CN bond is

been broken.

Reporting

Zinc has the function of messenger able to activate signaling paths. Many of these pathways reinforce the aberrant growth of cancer. One of the anticancer therapies involves the targeting of ZIP transporters (irt-like protein - zinc transporter protein). These are membrane transport proteins of the solute transporter family that control intra-membrane zinc delivery and regulate its intracellular and cytoplasmic concentrations.

Other Proteins

Zinc plays a structural role in the so-called "zinc finger" - or zinc fingers, specific protein regions capable of binding DNA. The zinc finger is a part of some transcription factors, proteins that recognize DNA sequences during replication and transcription processes.

The zinc finger zinc ions help to maintain the finger structure by binding in a coordinated way to four amino acids in the transcription factor. The transcription factor wraps the DNA helix and uses the various "finger" portions to bind accurately to the target sequence.

In blood plasma, zinc is bound and transported by albumin (60% - low affinity) and by transferrin (10%). The latter also carries iron, which reduces the absorption of zinc and vice versa. A similar antagonism also occurs between zinc and copper. The concentration of zinc in the blood plasma remains relatively constant regardless of oral intake - with food or supplements - of zinc. Cells in the salivary glands, prostate gland, immune system and intestines use zinc signaling to communicate with each other.

In some microorganisms, in the intestine and in the liver, zinc can be stored in metallothionein reserves. Intestinal cell MT is able to regulate the absorption of food zinc by 15-40%. However, inadequate or excessive intake can be harmful; in fact, due to the antagonism principle, excess zinc compromises the absorption of copper.

The human dopamine transporter contains a high affinity binding site for extracellular zinc which, once saturated, inhibits dopamine reuptake and amplifies amphetamine-induced dopamine efflux - in vitro. Human serotonin and norepinephrine transporters do not contain binding sites for zinc.

Bibliography

  • Maret, Wolfgang (2013). "Chapter 12. Zinc and Human Disease". In Astrid Sigel; Helmut Sigel; Roland KO Sigel. Interrelations between Essential Metal Ions and Human Diseases. Metal Ions in Life Sciences. 13. Springer. pp. 389-414.
  • Prakash A, Bharti K, Majeed AB (April 2015). "Zinc: indications in brain disorders". Fundam Clin Pharmacol. 29 (2): 131–149.
  • Cherasse Y, Urade Y (November 2017). "Dietary Zinc Acts as a Sleep Modulator". International Journal of Molecular Sciences. 18 (11): 2334. Zinc is the second most abundant trace metal in the human body, and is essential for many biological processes. ... The trace metal 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. It also plays a major role in cell signaling and modulation of neuronal activity.
  • Prasad AS (2008). "Zinc in Human Health: Effect of Zinc on Immune Cells". Mol. Med. 14 (5–6): 353–7
  • Zinc's role in microorganisms is particularly reviewed in: Sugarman B (1983). "Zinc and infection". Review of Infectious Diseases. 5 (1): 137–47.
  • Cotton 1999, pp. 625-629
  • Plum, Laura; Rink, Lothar; Haase, Hajo (2010). "The Essential Toxin: Impact of Zinc on Human Health". Int J Environ Res Public Health. 7 (4): 1342–1365.
  • Brandt, Erik G .; Hellgren, Mikko; Brinck, Tore; Bergman, Tomas; Edholm, Olle (2009). "Molecular dynamics study of zinc binding to cysteines in a peptide mimic of the alcohol dehydrogenase structural zinc site". Phys. Chem. Chem. Phys. 11 (6): 975–83
  • Rink, L .; Gabriel P. (2000). "Zinc and the immune system". Proc Nutr Soc. 59 (4): 541–52.
  • Wapnir, Raul A. (1990). Protein Nutrition and Mineral Absorption. Boca Raton, Florida: CRC Press.
  • Berdanier, Carolyn D .; Dwyer, Johanna T .; Feldman, Elaine B. (2007). Handbook of Nutrition and Food. Boca Raton, Florida: CRC Press.
  • Bitanihirwe BK, Cunningham MG (November 2009). "Zinc: the brain's dark horse". Synapse. 63 (11): 1029–1049.
  • Nakashima AS; Dyck RH (2009). "Zinc and cortical plasticity". Brain Res Rev. 59 (2): 347–73
  • 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. Pol. Pharm. 71 (3): 369–377. Archived (PDF) from the original on August 29, 2017.
  • PMID 17119290
  • NRC 2000, p. 443
  • Stipanuk, Martha H. (2006). Biochemical, Physiological & Molecular Aspects of Human Nutrition. WB Saunders Company. pp. 1043-1067.
  • Greenwood 1997, pp. 1224-1225
  • Kohen, Amnon; Limbach, Hans-Heinrich (2006). Isotope Effects in Chemistry and Biology. Boca Raton, Florida: CRC Press. p. 850.
  • Greenwood 1997, p. 1225
  • Cotton 1999, p. 627
  • Gadallah, MAA (2000). "Effects of indole-3-acetic acid and zinc on the growth, osmotic potential and soluble carbon and nitrogen components of soybean plants growing under water deficit". Journal of Arid Environments. 44 (4): 451–467.
  • Ziliotto, Silvia; Ogle, Olivia; Yaylor, Kathryn M. (2018). "Chapter 17. Targeting Zinc (II) Signaling to Prevent Cancer". In Sigel, Astrid; Sigel, Helmut; Freisinger, Eva; Sigel, Roland KO Metal-Drugs: Development and Action of Anticancer Agents. 18. Berlin: de Gruyter GmbH. pp. 507-529.
  • Cotton 1999, p. 628
  • Whitney, Eleanor Noss; Rolfes, Sharon Rady (2005). Understanding Nutrition (10th ed.). Thomson Learning. pp. 447-450
  • NRC 2000, p. 447
  • Hershfinkel, Michal; Silverman, William F .; Sekler, Israel (2007). "The Zinc Sensing Receptor, a Link Between Zinc and Cell Signaling". Molecular Medicine. 13 (7–8): 331–6.
  • Cotton 1999, p. 629
  • Blake, Steve (2007). Vitamins and Minerals Demystified. McGraw-Hill Professional. p. 242.
  • Fosmire, GJ (1990). "Zinc toxicity". American Journal of Clinical Nutrition. 51 (2): 225–7.
  • Krause J (April 2008). "SPECT and PET of the dopamine transporter in attention-deficit / hyperactivity disorder". Expert Rev. Neurother. 8 (4): 611–625.
  • Sulzer D (February 2011). "How addictive drugs disrupt presynaptic dopamine neurotransmission". Neuron. 69 (4): 628–649.
  • Scholze P, Nørregaard L, Singer EA, Freissmuth M, Gether U, Sitte HH (June 2002). "The role of zinc ion in reverse transport mediated by monoamine transporters". J. Biol. Chem. 277 (24): 21505–21513. The human dopamine transporter (hDAT) contains an endogenous high affinity Zn2 + binding site with three coordinating residues on its extracellular face (His193, His375, and Glu396). ... Thus, when Zn2 ​​+ is co-released with glutamate, it may greatly augment the efflux of dopamine.