Glutathione
(GSH)
Cystine is the preferred precursor for glutathione synthesis
Glutathione
(GSH) is a tripeptide - a chain of three amino acids - cysteine,
glycine, and glutamic acid - found in human cell tissue.
Glutathione
exists in the reduced form (GSH), and maintains a balance with
its oxidized form (GSSG) - a disulfide. GSH is our body's Master
Antioxidant.
Cysteine
- as a free amino acid - is potentially toxic and is spontaneously
catabolized or destroyed in the gastrointestinal tract and blood
plasma.
Hence
it does not represent an ideal delivery system to the cell.
However,
when it is present as a cysteine=cysteine dipeptide
- called cystine - (two cysteine molecules linked by a
disulfide bond) it is more stable than the free amino acid cysteine.
The di-peptide, cystine, travels safely through
the digestive tract and blood and is promptly broken up or reduced
to the two cysteine molecules when it enters the cell.
How
is Glutathione manufactured?
Glutathione
is synthesized inside your cells from the three amino acid precursors,
L-glutamate, L-cysteine, and L- glycine.
Glutathione
synthesis is a two-step process involving the enzymes gamma-glutamylcysteine
synthetase and GSH synthetase.
The
first reaction is the rate-limiting step and is effectively inhibited
by GSH feedback.
This
means the reaction is controlled by its own end-product
and slows down once enough glutathione is synthesised. The
second reaction is not subject to negative feedback by GSH.
When
GSH is consumed or used up in the neutralisation of harmful oxyradicals,
this feedback inhibition is lost.
So
now, the availability of L-cysteine as a precursor determines
how much glutathione is synthesised by the cell.
The
amount of cysteine available can hence become the rate-limiting
factor for the manufacture of glutathione.
If
cysteine levels drop, the body will convert methionine, another
amino acid, to cysteine, but then other systems run out of methionine,
which is needed for making protein.
Macrophages
(immune "scavenger" cells) and Astrocytes
(a category of brain cells that influence the activity of
neurons) prefer Cystine for manufacturing glutathione,
while Lymphocytes and Neurons prefer cysteine.
Optimizing
glutathione levels in macrophages and astrocytes with cystine
allows these cells to provide cysteine to lymphocytes and neurons
directly upon demand.
References:
The
systemic availability of oral glutathione
Witschi A, Reddy S, Stofer B, Lauterburg BH. [Eur J Clin
Pharmacol. 1992;43(6):667-9.]
Because of hydrolysis of glutathione by intestinal and hepatic
gamma-glutamyltransferase, dietary glutathione is not a major
determinant of circulating glutathione, and it is not possible
to increase circulating glutathione to a clinically beneficial
extent by the oral administration of a single dose of glutathione.
Also see:
From
Cell to Super-Cell - with Glutathione
Glutathione (GSH) - Master
Antioxidant and Cellular Detoxifier
Glutathione (GSH) & the
Immune System - Your Lifeline to Health
Un-denatured
Whey Protein - The Best Way to Raise Glutathione Levels
Diagram
of Glutathione synthesis Courtesy of Michael W. King, Professor
IU School of Medicine and IU Center for Regenerative Biology and
Medicine, Terre Haute, IN. 47809
Diagram
of Glutathione disulfide Courtesy of Michael W. King, Professor
IU School of Medicine and IU Center for Regenerative Biology and
Medicine, Terre Haute, IN. 47809
Diagrams
of Cysteine and Cystine molecules courtesy of Cystinuria.org
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