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Metallothionein expression in animals: a physiological perspective on

function.

SR, Cousins RJ

J Nutr 2000 May, 130:51085-8

[Related MEDLINE Records]

Abstract

An integration of knowledge concerning regulation of metallothionein

expression with research on metallothionein's proposed functions is necessary

to delineate how this metalloprotein affects cellular processes, especially

zinc metabolism. Metallothionein expression is driven by a number of

physiological mediators through several response elements in the

metallothionein gene promoter. Cellular accumulation of metallothionein

depends on both gene expression and protein degradation. Both depend largely

on availability of cellular zinc derived from the dietary zinc supply.

Metallothionein expression is related to zinc accumulation in certain organs.

Evidence has been produced, which suggests that metallothionein could act in

a number of biochemical processes. It may act in zinc trafficking and/or zinc

donation to apoproteins, including zinc finger proteins that act in cellular

signaling and transcriptional regulation. As a result, metallothionein

expression may affect a number of cellular processes including gene

expression, apoptosis, proliferation and differentiation. The ability of

metallothionein to exchange other metals with zinc in these proteins may

explain a role in metal toxicity. Similarly, mobilization of zinc from

metallothionein by oxidative stresses may explain its proposed antioxidant

function. Apparent good health of metallothionein-deficient mice argues

against a critical biological role for metallothionein; however, expression

may be critical in times of stress.

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  • 7 months later...
  • 3 months later...

They identify the metallothionein gene and genes in the surrounding chromosomal

region (I'm not sure how many copies there are of the gene in the human genome)

and sequence that region. The sequence of the metalliothionein genes of

autistics w/ Mercury toxicity is compared to that of normal kids. The DNA can

be isolated from a blood sample. If there is enough data on the Hg-binding

region of the metallothionein gene, then researchers may be able to pinpoint

mutations that could block mercury detoxification. Most likely, this

information is not yet available. So, the best one could hope for is to find

mutations that consistently occur in the " autistic children " subgroup. Hope

this helps!

God Bless,

S. Hooker, Ph.D., P.E.

Director of Research

PhytaGenics

902 Battelle Blvd., MSIN K2-10

Richland, WA 99352

Phone: 509-375-4420

FAX: 509-372-4660

email: brian.hooker@...

[ ] Re: metallothionein

OK, but how do you test for this? Any web references that go into

technicalities?

>They are looking in anomolies in the genetic sequence of metallothionein

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,

I thought that 'genetic' defect was only one of the reasons for defective MT

functioning, and that a toxic metal overload is a factor which disables MT

protein functioning. Also that impaired GSH synthesis disrupts MT

functioning in brain and gut.

Celia

[ ] Re: metallothionein

>

>

> OK, but how do you test for this? Any web references that go into

> technicalities?

>

>

>

> >They are looking in anomolies in the genetic sequence of metallothionein

>

>

>

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Would prove interesting if they did before and after with mercury-toxic

individuals who then detox...or compare before and after vaccines of the same

child (taking multi-generational accumulation into account)...

S

On Thu, 04 October 2001, " Hooker, S " wrote:

>

> <html><body>

> <tt>

> They identify the metallothionein gene and genes in the surrounding

chromosomal<BR>

> region (I'm not sure how many copies there are of the gene in the human

genome)<BR>

> and sequence that region. & nbsp; The sequence of the metalliothionein genes

of<BR>

> autistics w/ Mercury toxicity is compared to that of normal kids. & nbsp; The

DNA can<BR>

> be isolated from a blood sample. & nbsp; If there is enough data on the

Hg-binding<BR>

> region of the metallothionein gene, then researchers may be able to

pinpoint<BR>

> mutations that could block mercury detoxification. & nbsp; Most likely, this<BR>

> information is not yet available. & nbsp; So, the best one could hope for is to

find<BR>

> mutations that consistently occur in the & quot;autistic children & quot;

subgroup. & nbsp; Hope<BR>

> this helps!<BR>

> <BR>

> God Bless,<BR>

> <BR>

> <BR>

> <BR>

> <BR>

> S. Hooker, Ph.D., P.E.<BR>

> <BR>

> Director of Research<BR>

> <BR>

> PhytaGenics<BR>

> <BR>

> 902 Battelle Blvd., MSIN K2-10<BR>

> <BR>

> Richland, WA & nbsp; 99352<BR>

> <BR>

> Phone: & nbsp; 509-375-4420<BR>

> <BR>

> FAX: & nbsp; & nbsp; & nbsp; 509-372-4660<BR>

> <BR>

> email: & nbsp; brian.hooker@...<BR>

> <BR>

> [ ] Re: metallothionein<BR>

> <BR>

> <BR>

> OK, but how do you test for this? & nbsp; Any web references that go into <BR>

> technicalities?<BR>

> <BR>

> <BR>

> <BR>

> & gt;They are looking in anomolies in the genetic sequence of

metallothionein<BR>

> <BR>

> <BR>

>

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Okay, well, this is all fine, but I wonder if they are also

testing mercury toxic adults who are NT (or at least not

dx as ASD). I think this would make a very good point of

comparison.

>They identify the metallothionein gene and genes in the surrounding

chromosomal

>region (I'm not sure how many copies there are of the gene in the human

genome)

>and sequence that region. The sequence of the metalliothionein genes of

>autistics w/ Mercury toxicity is compared to that of normal kids. The DNA

can

>be isolated from a blood sample. If there is enough data on the Hg-binding

>region of the metallothionein gene, then researchers may be able to pinpoint

>mutations that could block mercury detoxification. Most likely, this

>information is not yet available. So, the best one could hope for is to find

>mutations that consistently occur in the " autistic children " subgroup. Hope

>this helps!

>

>God Bless,

>

>

>

>

> S. Hooker, Ph.D., P.E.

>

>Director of Research

>

>PhytaGenics

>

>902 Battelle Blvd., MSIN K2-10

>

>Richland, WA 99352

>

>Phone: 509-375-4420

>

>FAX: 509-372-4660

>

>email: brian.hooker@...

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>>Would prove interesting if they did before and after with

>>mercury-toxic individuals who then detox...or compare before and

>>after vaccines of the same child (taking multi-generational

>>accumulation into account)...

S

On Thu, 04 October 2001, " Hooker, S " wrote:

>

> <html><body>

> <tt>

> They identify the metallothionein gene and genes in the surrounding

>chromosomal<BR>

> region

See, I still don't get this. Looking at the DNA for this gene would

NOT give any info about the actual function of the protein.

Certainly, the genes would not change with chelation...

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  • 1 month later...

<<<<<How does one increase the amount of metallothionein in a child's

body? Al.>>>>>

Al, I am just reading about this to try to find out how to test for it. I

read that metallothionein (MT) dysfunction causes Cu/Zn imbalance, with

high Cu and low Zn. How do you know you need to increase it?

My son's DDI hair test shows just the opposite of high Cu/low Zn his

ratio was 24.6; just a little higher than the reference range for zinc

with Cu within reference range.

Dr. Walsh of Pfieffer Institute in Chicago said at the DAN

conference that of their testing of autistics 15% were over methylated &

need folic acid and 45% were undermethylated & needed eSam.

Does it sound like if one is high in Cu that the body needs eSam and if

the body is high in Zn it needs folic acid?

Also trying to figure it out,

Sharon in Virginia

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Msdai54513@... wrote:

> In a message dated 11/11/01 4:41:33 PM Pacific Standard Time,

> askeralkris@... writes:

>

>

> >

> >

> > How does one increase the amount of metallothionein in a child's

> body?

> >

> > I woul.d like to know that too. If you find out, please let me

> know.

>

> angela

>

>

The following is from someone's notes of the last DAN conference that

got posted here back in October

" The activity of metallothionein is primarily enhanced by zinc,

glutathione, selenium, and n-acetyl cysteine. Of secondary benefit are

vitamins B6, A, C, D, E, genistein, biochanin A, and glucorticoids. "

Here is the entire set of notes for Dr Walsh's presentation

Disordered Metal Metabolism: Walsh - Walsh first

discussed his data on 503 children with autism, which found an elevated

Cu:Zinc ratio in nearly all the children. Specifically, 85% had very

high Cu:Zinc ratios, 8% were receiving zinc supplements and had only

moderate imbalances, 6% has a severe pyrole disorder (indicating severe

zinc depletion), and only 4 of the 503 children did not have a serious

Cu:zinc imbalance. The average Cu:zinc ration was 1.63 in autism, vs

1.15 in the controls, and was highly statistically significant

(p<0.0001). This is a very important finding from a very large study.

Walsh hypothesizes that the Cu:Zinc imbalance could be due to a defect

in metallothionein function, since metallothionein proteins regulate Cu

and Zinc levels. The primary functions of metallothionein include:

development of brain neurons; cell transcription; regulation of Cu and

Zinc; detoxification of heavy metals; maturation of GI tract; powerful

antioxidant; immune function; deliver of zinc to cells. It is the

primary defense of the body against heavy metals. If a defect in

metallothionein exists, it could be due to a genetic impairment or due

to environmental damage. There are four metallothionein proteins: MT-I

and MT-2 are present in all cells throughout the brain and periphery

MT-III is a neuronal growth inhibitor found primarily in brain MT-IV is

found primarily in skin and GI tract. A defective metallothionein could

explain many of the symptoms of autism, including sensitivity to heavy

metals, zinc depletion and copper overload, reduced stomach acid,

incomplete breakdown of proteins. Since metallothionein production is

enhanced by estrogen and progesterone during early development, females

will be better protected than males against heavy metals. Researchers

studied a MT-knockout mouse (a mouse without any metallothionein) and

found that it had a very weakened immune system and had a high incidence

of seizures. The activity of metallothionein is primarily enhanced by

zinc, glutathione, selenium, and n-acetyl cysteine. Of secondary benefit

are vitamins B6, A, C, D, E, genistein, biochanin A, and glucorticoids.

In s disease, copper overload can be treated by removing excess

copper and long-term zinc therapy. This may also help in autism, and may

lead to reduced GI problems, improved behavior and cognition, and

reduced vulnerability to heavy metals. His lab (Pfeiffer Labs) is

investigating nutritional interventions to promote metallothionein and

thereby reduce symptoms of autism. However, there are no commercial lab

tests for metallothionein, and the children with autism did not have

their metallothionein levels tested. Also, their lab found that 45% of

children with autism were undermethylated (needed folate and DMAE),

whereas 15% were overmethylated. Conclusion: In a very large and

important study of 503 children with autism, a very high copper:Zinc

ratio was found. This could have a wide-reaching effect since copper and

zinc play many roles in the body. It is hypothesized that the Cu:Zn

imbalance is due to a defect in metallothionein, and such a defect could

explain many of the biochemical abnormalities in autism. Nutritional

interventions with zinc and other supplements are recommended for

treating this imbalance.

--

" When you don’t know where you’re going, you have

to stick together just in case someone gets there. "

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i'd also like to know the answer to this, as SAM-e is something we used to give

but stopped when the pills, at over one dollar apiece, began to smell 'off'. if

necessary, but on,y if necessary, i'd give them again, but get a new batch.

julie

Re: [ ] Metallothionein

<<<<<How does one increase the amount of metallothionein in a child's

body? Al.>>>>>

Al, I am just reading about this to try to find out how to test for it. I

read that metallothionein (MT) dysfunction causes Cu/Zn imbalance, with

high Cu and low Zn. How do you know you need to increase it?

My son's DDI hair test shows just the opposite of high Cu/low Zn his

ratio was 24.6; just a little higher than the reference range for zinc

with Cu within reference range.

Dr. Walsh of Pfieffer Institute in Chicago said at the DAN

conference that of their testing of autistics 15% were over methylated &

need folic acid and 45% were undermethylated & needed eSam.

Does it sound like if one is high in Cu that the body needs eSam and if

the body is high in Zn it needs folic acid?

Also trying to figure it out,

Sharon in Virginia

=======================================================

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