Metallothionein
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Metallothioneins are proteins whose purpose is to metabolise and regulate metals. There are at least ten known closely related metallothionein proteins expressed in humans. In the human body, large quantities are synthesised primarily in the liver and kidneys. Its production is dependent on availability of the dietary minerals zinc and selenium, and the amino acids histidine and cysteine.
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Function
Metallothionein proteins participate in the uptake, transport, and regulation of zinc in a biological system. The zinc binding sites are typically cysteine-rich, and often bind three or four zinc ions. In some proteins, histidine also participates in zinc binding. By binding and releasing zinc, metallothioneins (MTs) regulate its level within the body. Zinc, in turn, is a key element for the activation and binding of certain transcription factors through its participation in (aptly-named) zinc fingers. Metallothionein also carries zinc ions (signals) from one part of the cell to another. When zinc enters a cell, it can be picked up by thionein (which thus becomes "metallothionein") and carried to another part of the cell where it is released to another organelle or protein. In this way the thionein-metallothionein becomes a key component of the zinc signaling system in cells. This system is particularly important in the brain, where zinc signaling is prominent both between and within nerve cells. It also seems to be important for the regulation of the tumor suppressor protein p53.
Metallothionein (MT) detoxifies mercury and heavy metals by binding to the metal before it can cause harm. It forms subcellular inclusions or crystals which act jointly to consolidate and enclose excess metals. These inclusions then accumulate within tissues or skeletal structure over time.
Metallothionein and disease
Cancer
Because MTs play an important role in transcription factor regulation, problems with MT function or expression may lead to malignant transformation of cells and ultimately cancer. Studies have found increased expression of MTs in some cancers of the breast, colon, kidney, liver, lung, nasopharynx, ovary, prostate, mouth, salivary gland, testes, thyroid and urinary bladder; they have also found lower levels of MT expression in hepatocellular carcinoma and liver adenocarcinoma.
There is evidence to suggest that higher levels of MT expression may also lead to resistance to chemotherapeutic drugs.
Autism
In a 2001 presentation to the American Psychiatric Association, Dr. William J. Walsh of the Pfeiffer Treatment Center suggested a potential link between metallotionein disorders and autism. Walsh concluded
- "The absence of Cu and Zn homeostasis and severe Zn deficiency are suggestive of a metallothionein (MT) disorder. MT functions include neuronal development, detoxification of heavy metals, and immune response. Many classic symptoms of autism may be explained by a MT defect in infancy including G.I. tract problems, heightened sensitivity to toxic metals, and abnormal behaviors. These data suggest that an inborn error of MT functioning may be a fundamental cause of autism."[1]
This study has brought to light a possible mechanism for an increase of autism cases claimed by some to be associated with the use of thimerosal in vaccines.
External links
- Cherian MG, Jayasurya A, Bay BH. (2003) "Metallothioneins in human tumors and potential roles in carcinogenesis" Mutation Research 533(1-2):201-209.