What can disrupt iron metabolism was Re: STAN: odd toenails

[Guest guest]

Hi, everybody interested in the iron angle,

One thing that can really tie up iron is oxalate. It forms a shell around

iron, making the iron inaccessible.

I tried to find a picture of this complex for you but it is no longer on

the net, but a picture of iron oxalate is on the third page of my AutismOne

presentation from

2006: http://autismone.org/uploads/2006/Owens%20%20Powerpoint%20USE.ppt

Oxalate also disables the iron transport molecule called transferrin. The

reason it disables the molecule is that oxalate looks so much like

carbonate chemically that it slips into the transferrin molecule and

replaces the usual carbonate ion which binds iron. When it sneaks into

this molecule, it still succeeds in loading up iron into transferrin, but

it binds so tightly that it won't let go or the iron when it is supposed

to! The net effect is a buildup of iron bound to transferrin

intracellularly, but no delivery of iron to the appropriate places in the

cell, so the iron cannot become part of haem.

Here is a picture showing transferrin bringing iron into the cell to be

released:

http://www.nature.com/nrm/journal/v6/n4/images/nrm1620-f4.jpg

This might also hurt the activity of the citric acid cycle in the enzyme

aconitase which is also an iron regulatory protein.

See this site:

http://biocurious.com/molecule-of-the-month-aconitase-and-iron-regulatory-protei\

n-1

and this one:

http://www.bmb.leeds.ac.uk/illingworth/metabol/krebs.htm

If oxalate is trapping iron in transferrin, the iron level would build up

but the iron couldn't be utilized and a lot of iron regulation would be

worthless. I've wondered if this issue were studied in hemachromatosis as

I've seen no evidence that people are aware of this aspect of oxalate which

is reported very clearly in the article below.

If oxalate is the culprit driving deficiency symptoms, then taking more

iron wouldn't help, but reducing your exposure to oxalate in the diet would

help. We've had people report a resolution of anemia not long into the

diet who had been taking iron before without having it resolve the anemia.

If you need help in figuring out which foods your child eats that might be

high oxalate, then take a look at the listings here:

http://lowoxalate.info/food_lists/alph_oxstat_chart.pdf

I hope this helps.

J Mol Biol. 2004 May 21;339(1):217-26.

The oxalate effect on release of iron from human serum transferrin explained.

Halbrooks PJ,

Mason AB,

TE,

Briggs SK,

Everse SJ.

Department of Biochemistry, College of Medicine, University of Vermont, 89

Beaumont Avenue, Burlington, VT 05405, USA.

A unique feature of the mechanism of iron binding to the transferrin (TF)

family is the synergistic relationship between metal binding and anion

binding. Little or no iron will bind to the protein without concomitant

binding of an anion, physiologically identified as carbonate. Substitution

of oxalate for carbonate produces no significant changes in polypeptide

folding or domain orientation in the N-lobe of human serum TF (hTF) as

revealed by our 1.2A structure. The oxalate is able to bind to the iron in

a symmetric bidentate fashion, which, combined with the low pK(a) of the

oxalate anion, makes iron displacement more difficult as documented by both

iron release kinetic and equilibrium data. Characterization of an N-lobe in

which the arginine at position 124 is mutated to alanine reveals that the

stabilizing effect of oxalate is even greater in this mutant and nearly

cancels the destabilizing effect of the mutation. Importantly,

incorporation of oxalate as the synergistic anion appears to completely

inhibit removal of iron from recombinant full-length hTF by HeLa S(3)

cells, strongly indicating that oxalate also replaces carbonate in the

C-lobe to form a stable complex. Kinetic studies confirm this claim. The

combination of structural and functional data provides a coherent

delineation of the effect of oxalate binding on hTF and rationalizes the

results of many previous studies. In the context of iron uptake by cells,

substitution of carbonate by oxalate effectively locks the iron into each

lobe of hTF, thereby interfering with normal iron metabolism.

PMID: 15123433 [PubMed - indexed for MEDLINE]

Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5622-6. Epub 2002 Apr 9.[] [] Links

Iron uptake from plasma transferrin by the duodenum is impaired in the Hfe

knockout mouse.

Trinder D, Olynyk JK, Sly WS, EH.

Department of Medicine, University of Western Australia and Western

Australian Institute for Medical Research, Perth 6009, Western Australia,

Australia. dtrinder@...

Hereditary hemochromatosis (HH) is a disorder of iron metabolism in which

enhanced iron absorption of dietary iron causes increased iron accumulation

in the liver, heart, and pancreas. Most individuals with HH are homozygous

for a C282Y mutation in the HFE gene. The function of HFE protein is

unknown, but it is hypothesized that it acts in association with

beta(2)-microglobulin and transferrin receptor 1 to regulate iron uptake

from plasma transferrin by the duodenum, the proposed mechanism by which

body iron levels are sensed. The aim of this study was to test this

hypothesis by comparing clearance of transferrin-bound iron in Hfe knockout

(KO) mice with that observed in C57BL/6 control mice. The mice were fed

either an iron-deficient, control, or iron-loaded diet for 6 weeks to alter

body iron status. The mice then were injected i.v. with (59)Fe-transferrin,

and blood samples were taken over 2 h to determine the plasma (59)Fe

turnover. After 2 h, the mice were killed and the amount of radioactivity

in the duodenum, liver, and kidney was measured. In both Hfe KO and C57BL/6

mice, plasma iron turnover and iron uptake from plasma transferrin by the

duodenum, liver, and kidney correlated positively with plasma iron

concentration. However, duodenal iron uptake from plasma transferrin was

decreased in the Hfe KO mice compared with the control mice. Despite this

difference in duodenal uptake, the Hfe KO mice showed no decrease in iron

uptake by the liver and kidney or alteration in the plasma iron turnover

when compared with C57BL/6 mice. These data support the hypothesis that HFE

regulates duodenal uptake of transferrin-bound iron from plasma, and that

this mechanism of sensing body iron status, as reflected in plasma iron

levels, is impaired in HH.

PMID: 11943867 [PubMed - indexed for MEDLINE]

At 05:13 PM 2/6/2008, you wrote:

>I'm freaked out now too. More stuff to worry about. Amazing how many

>responses have been posted since I asked about the odd toenails.

>

>STAN, any input?????

>

>

>

> Re: Christel: odd toenails here too....

>

>sorry to jump in but my son has concave nails too so this really

>caught my attention. I looked it up on wikipedia

>

>Koilonychia is a nail disease that can be a sign of iron-deficiency

>anemia.[1] Koilonychia literally means " spoon nails. " It refers to

>nails (usually of the hand) which have lost their convexity, becoming

>flat or even concave in shape. In a sense, koilonychia is the opposite

>of nail clubbing.

>

>Koilonychia is associated with Plummer-Vinson syndrome.

>The Plummer-Vinson syndrome, also called Paterson-Brown- syndrome

>or sideropenic dysphagia is a disorder linked to severe, long-term

>iron deficiency anemia, which causes swallowing difficulty (dysphagia)

>due to web-like membranes of tissue growing in the throat (esophageal

>webs). P-VS sufferers often complain of a burning sensation with the

>tongue and oral mucosa, and atrophy of lingual papillae produces a

>smooth, shiny red tongue dorsum. The cause of Plummer-Vinson syndrome

>is unknown; however, genetic factors and nutritional deficiencies may

>play a role. Women are at higher risk than men, particularly in middle

>age. In these patients, esophageal squamous cell carcinoma risk is

>increased; therefore, it is considered a premalignant process.

>

>my son has recently begun having swallowing trouble which I assume was

>due to sensory issues. I've avoided iron supplementation in the last

>while because we have a family history of hemochromotosis. But now I

>am officially freaked out.

>Kes

>

> >

> > > How did you get the accurate diagnosis that the

> > > yeast was in his

> > > bloodstream? My son has the curling up at both

> > > ends tonnails too. What

> > > was yor strategy for dealing with the yest in

> > > the bloodstream? Thanks

> > > Di

> > >

> > >

> >

> >

> >

> >

>__________________________________________________________

> > Be a better friend, newshound, and

> > know-it-all with Yahoo! Mobile. Try it now.

>http://mobile.yahoo.com/;_ylt=Ahu06i62sR8HDtDypao8Wcj9tAcJ

> >

>

>

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