Glutathione as a Chelator of heavy metals

[Guest guest]

WHY GLUTATHIONE IS A CHELATOR OF HEAVY METALS

(taken from The Detoxx Book by MD, Kane MD, and

Neal Speight MD)

In Chapter 7 of the Doctor's Book they say that Glutathione (GSH)

performs many vital physiological and metabolic functions within all

cells. It is a potent reducing agent with many actions at the

molecular, cellular and tissue levels because of its impact as a

systemic anti-toxin. They think that the glutathione status of a

cell, the excess of reduced glutathione (GSH) over oxidized

glutathione (GSSG) may be one of the most accurate indicators of

cellular health.

GSH is the most abundant nonprotein thiol in the body and it provides

the reactive thiol (SH) group which is responsible for the varied

functions of GSH which include –

• Maintenance of protein structure and function

• Regulation of protein synthesis and degradation

• Stabilisation of immune function

• Protection against oxidative damage

• DETOXIFICATION OF REACTIVE CHEMICALS

GSH also serves as a storage and transport functions in –

• Leukotriene and prostaglandin metabolism

• Reduction of ribonucleotides to deoxyribonucleotides

• Modulation of microtubule-related processes

• Formation of bile

GSH is a tripeptide formed by linking 2 amino-acids, L-glutamate, L-

cysteine and glycine. The liver is the major site of biosynthesis of

GSH and has the greatest concentration of it followed by the spleen,

kidney, lens, erythrocytes and leukocytes.

It is a complicated system that keeps GSH in the form that enables it

to perform the vital functions mentioned above; oxidant stress will

overwhelm the system and stop it from working leading to the

depletion of the intracellular pool of GSH. It can also be depleted

when GSH is conjugated to foreign compounds.

Proteins may be activated or inhibited by the exchange between

protein and GSH.

GSH plays a major role in detoxifying many reactive metabolites by

binding to endogenous compounds which serves to –

• Limit and regulate the reactivity of chemicals

• Facilitate membrane transport and elimination from the cell

• May lead to the formation of essential biological mediators

GSH forms metal complexes via non-enzymatic reactions. It plays a

crucial role in metal transport, storage and metabolism being one of

the most versatile metal binding ligands in the body. GSH contains 6

potential co-ordination sites for metal binding; the cysteinyl

sulfhydryl, the glutamyl amino, the glycl and glutamyl carboxyl

groups and 2 peptide linkages.

Mercury may bind to a variety of enzyme systems with a particular

affinity for ligands containing sulfhydryl groups. GSH is the major

dialyzable methyl mercury binding substance in the brain and may bind

up to 30% of cellular methylmercury.

A considerable amount of methymercury is excreted into bile when

adequate concentration biliary GSH is available thus the primary

mechanism for removal of mercury is through its bond with GSH via

bile, however a sluggish biliary flow due to biliary congestion

renders an impaired elimination of Hg.

Oral loading of L-cystine and N-acetyl cysteine (NAC) would be

contraindicated in the mercury compromised patient in that these

compounds may facilitate redistribution of mercury from tissues

throughout the body and exacerbate the adverse neurological impact of

mercury.

However the supplementation of branched chain amino acids and L-

Phenylaline would be supportive to the metal toxic patient and

inhibit the transport of the methylmercury complex across the blood

brain barrier. Although the oral use of methionine might be

considered in patients with disturbed methylation pathways, as is

often the case in states of neurotoxicity, methionine may stimulate

homocystine synthesis. In addition the use of methionine can

suppress the release of GSH from the liver.

Neurotoxins may present in tandem as pathogenic and heavy metal

burdens as mercury, lead, cadmium and arsenic. Both pathogenic and

heavy metals are lipid soluble and may reside in the liver and

biliary tree. Removal of mercury is challenging due to its

lipophilic nature.

The administration of DMPS and DMSA can mobilize heavy metals such as

mercury yet may cause serious side effects in patients with

neurological involvement.

Conversely the use of an IV Glutathione fast push can safely and

efficiently relieve the body burden of heavy metals, biotoxins,

endogenous and exogenous toxins.

(My question is will other forms of GSH such as lipoceutical GSH do

the same thing?)

Pam