MT was discovered in 1957 by Vallee and Margoshe from purification of a Cd-binding protein from horse (equine) renal cortex.[3] MT plays a role in the protection against metal toxicity and oxidative stress, and is involved in zinc and copper regulation.[4] There are four main isoforms expressed in humans (family 1, see chart below): MT1 (subtypes A, B, E, F, G, H, L, M, X), MT2, MT3, and MT4. In the human body, large quantities are synthesised primarily in the liver and kidneys. Their production is dependent on availability of the dietary minerals such as zinc, copper, and selenium, as well as the amino acids histidine and cysteine.
Metallothioneins are rich in thiols, causing them to bind a number of trace metals. Metallothionein is one of the few eukaryotic proteins playing a substantial role in metal detoxification. Zinc and Cadmium are tetrahedrally coordinated to cysteine residues, and each metallothionein protein molecule may bind up to 7 atoms of Zn or Cd.[5] The biosynthesis of metallothionein appears to increase several-fold during periods of oxidative stress to shield the cells against cytotoxicity and DNA damage. Metallothionein biosynthesis can also be induced by certain hormones, pharmaceuticals, alcohols, and other compounds.[6] Metallothionein expression is upregulated during fetal development, particularly in liver tissue.[7]
^PDB: 2KAK; Peroza EA, Schmucki R, Güntert P, Freisinger E, Zerbe O (March 2009). "The beta(E)-domain of wheat E(c)-1 metallothionein: a metal-binding domain with a distinctive structure". Journal of Molecular Biology. 387 (1): 207–18. doi:10.1016/j.jmb.2009.01.035. PMID19361445.
^Sigel H, Sigel A, eds. (2009). Metallothioneins and Related Chelators (Metal Ions in Life Sciences). Vol. 5. Cambridge, England: Royal Society of Chemistry. ISBN978-1-84755-899-2.
^Margoshes M, Vallee BL (1957). "A cadmium protein from equine kidney cortex". Journal of the American Chemical Society. 79 (17): 4813–4814. doi:10.1021/ja01574a064.
^Felizola SJ, Nakamura Y, Arata Y, Ise K, Satoh F, Rainey WE, Midorikawa S, Suzuki S, Sasano H (September 2014). "Metallothionein-3 (MT-3) in the human adrenal cortex and its disorders". Endocrine Pathology. 25 (3): 229–35. doi:10.1007/s12022-013-9280-9. PMID24242700. S2CID39871076.