Start of the Glyteine® (GGC) story.
When working for a global baker's yeast manufacturer in 1997, Prof Wallace Bridge, UNSW Sydney was exploring manufacturing options for the production of glutathione as a value-added product. Through this project he developed an understanding of glutathione biochemistry which ultimately led to his interest in gamma-glutamylcysteine's (Glyteine®) benefits.
What is glutathione and where does it come from?
Glutathione is often termed the "master antioxidant". It is produced in every cell of your body. It is a tripeptide (small protein) that mops up free radicals. Glutathione's tripeptide (small protein) structure is composed of the amino acids (protein building blocks); glutamate, cysteine, and glycine. Glutathione is synthesized in two reactions inside each of our cells. The first joins glutamate and cysteine to form gamma-glutamylcysteine (Glyteine®) and the second adds glycine to form glutathione*.
How is glutathione produced in the body?
Glutathione is produced in every cell of our bodies. The system involves two enzymes (catalysts) that sequentially join the three amino acids glutamate, cysteine and glycine to form glutathione. The first enzyme (glutamate cysteine ligase, GCL) joins glutamate and cysteine to form gamma-glutamylcysteine (GGC, Glyteine®) and the second enzyme glutathione synthase adds the glycine to make glutathione. Both these reactions require energy (ATP), which is provided on the most part by the mitochondria. The video explains how glutathione levels are maintained (regulated) in cells at optimum (homeostasis) levels and the implications if this system goes wrong*.
Glutathione depletion and oxidative stress
Oxidative stress can occur if the capacity of our cells to produce enough glutathione is diminished and free radicals generated during mitochondrial respiration are not neutralized.
What about GLYTEINE®?
Animal and human studies have demonstrated that GLYTEINE® supplements can, as theoretically expected, increase cellular glutathione levels following a single dose. Clinical trials are currently underway to determine the efficacy of GLYTEINE® in numerous glutathione depletion related conditions*.
How quickly can Glyteine® (GGC) increase my glutathione levels?
A human clinical study has demonstrated that a single orally administered dose of GLYTEINE® could increase cellular (lymphocyte) glutathione levels above homeostasis within hours. This observation indicated that GLYTEINE® is systemically bioavailable by surviving the gastrointestinal tract, being distributed throughout the body by the vascular system, where it is taken up by cells and converted to glutathione. This finding highlights GLYTEINE®'s benefits.
Why haven't we heard of GLYTEINE® before?
Unlike NAC and glutathione there is no natural source that contains sufficient GLYTEINE® from which it can be extracted and processed. Though GLYTEINE® is continuously produced in almost every oxygen using cell from bacteria, through to plants and animals, it is almost always immediately converted to glutathione. So, the main reason, you have not been able to buy GLYTEINE® containing supplements is that no one until now has been able to work out a way to produce it. Our GLYTEINE® manufacturing process was developed purposefully over the last 20 years so that it so that it make the world a better place and not simply as a means of value adding to existing products.
What foods contain Glyteine® (GGC)?
Some foods contain gamma-glutamylcysteine (GGC), though GGC is produced in all food sources it is usually immediately converted into glutathione. The implications for developing a process for GGC (Glyteine®) manufacture are explained in the corresponding video.
Which foods naturally contain Glyteine® (GGC)?
Two major inarguable food sources in nature, egg white and fresh milk, contain small amounts of GGC, which would be of benefit to the glutathione levels of the growing baby animals.
Why should I care?
If our cells do not have enough glutathione to deal with the free radicals and toxins then they will be damaged, lose their physiological function, and perhaps even die.
When would I not produce enough glutathione?
Generally, there are two situations where you might not produce enough glutathione to protect your cells. The first is when you have an severe glutathione deficiency due to exposure to high levels of toxins (e.g. drug overdose) or free radicals (e.g. excessive exercise).
The second is an on-going deficiency that occurs when some of your cells (e.g. specific tissues or organs) permanently lose the ability to produce enough gamma-glutamylcysteine (GGC, Glyteine®), and hence glutathione, to protect themselves against normal levels of toxins and free radicals.
If my cells don't have enough glutathione – what can I do about it?
You can assist your body restore glutathione to normal levels by taking NAC and glutathione itself. Of the three amino acids that comprise glutathione, cysteine is the first one to run out during low glutathione levels. Glutathione is produced by two sequential enzyme catalyzed reactions. The first reaction combines glutamic acid with cysteine to produce GLYTEINE® (gammaglutamylcysteine) and is catalyzed by the enzyme, glutamate cysteine ligase (GCL). The second reaction adds glycine to GLYTEINE® to make glutathione and is catalyzed by the enzyme glutathione synthetase (GS). It is the GCL enzyme that impacts normal gamma-glutamylcysteine production. The solution seems obvious! – just provide GLYTEINE® to the cells.*
What are the benefits of eating glutathione rich foods?
Glutathione rich foods are simply sources of the building blocks (in particular, cysteine) for glutathione synthesis. The glutathione in these foods will not, however, be able to directly increase the glutathione levels inside your cells above homeostasis. The implication being that if you wish to boost your glutathione levels then dietary glutathione whether in a food or a supplement is not likely to help.
How is glutathione produced?
Glutathione is manufactured industrially using baker's yeast which is analogous to how we synthesise glutathione in our cells.
What is the difference between NAC vs glutathione vs Glyteine® (GGC)?
There are some supplement options for increasing glutathione levels Both NAC and glutathione (glutathione is broken down to its component amino acids by cells during cellular uptake) are simply cysteine sources for cells. This cysteine feeds into the damaged GCL enzyme and as such cannot increase GGC and hence glutathione levels. GLYTEINE® (GGC), on the other hand, can feed directly into the second enzyme where it is converted into glutathione*.
Glutathione supplements – do they work?
Glutathione from your diet either through food or supplements does not increase the glutathione content of your cells. Cells have up to one thousand-fold higher levels of glutathione than that of blood plasma. To overcome this concentration gradient, cells break down extracellular glutathione to its constituent amino acids, which are then taken up by the cell. Once inside, the glutathione is re-synthesized. This means, glutathione is just another source of cysteine that feeds into the damaged GCL enzyme and like NAC can do nothing to overcome the gammaglutamylcysteine (GGC) deficiency.
How does glutathione become depleted?
Severe glutathione depletion can be brought on by sudden and high-level exposure to conditions that overwhelm the body's capacity to produce glutathione. These include toxins, overdoses with drugs such as acetaminophen/paracetamol and even excessive exercise. Persistent glutathione depletion results from an inabilityin the capacity of cells to produce enough gamma glutamyl cysteine (GGC, Glyteine®). Cysteine prodrugs such as N-acetylcysteine (NAC) are noted to be of benefit for treating severe glutathione depletion and Glyteine® is introduced for its potential to address both severe and on-going permanent glutathione depletion.
Is glutathione depletion a problem for athletes during strenuous exercise?
Athletes run the risk of being repeatedly exposed to severe glutathione depletion and its associated oxidative stress.
How does glutathione homeostasis work?
There is a complex regulatory system that controls glutathione levels inside our cells. Each cell has its own optimum level (homeostasis) which has been determined by the evolutionary processes of nature. Glutathione homeostasis is maintained by a feedback inhibition system exerted by glutathione on the enzyme responsible for gamma-glutamylcysteine (GGC, Glyteine®) production. When glutathione is near homeostasis, the enzyme's activity is low and as glutathione gets used up, its activity increases.
How does low glutathione levels lead to oxidative stress?
Repeated exposure to oxidative stress can result in an accumulation of permanent damage to cells and their progeny. In many diseases and disorders, the first enzyme (glutamate cysteine ligase, GCL) involved in the synthesis of glutathione, which makes gamma glutamylcysteine (GGC, Glyteine®) becomes dysfunctional, which leads to lowered glutathione (homeostasis) levels that are too low to protect against oxidative stress. The nature of how the GCL enzyme becomes dysfunctional is the subject of ongoing research.
Can alcohol consumption deplete glutathione levels?
Alcohol consumption can deplete(lower) glutathione levels beyond normal.
Can I measure glutathione in my body?
The determination of glutathione levels is much more complex than it is for testing other important chemicals such as glucose.
What diet is best for glutathione?
With a lot of discussion on calorie restriction, and the different diets in the context of glutathione and human health, the key point that is raised is the difficulty for us to know what food is good for us. We cannot test the quality of our diet in animal models because the one thing that differentiates all animals is their diet. Through civilization we have lost our natural instinct for what is good for us, and from 10,000 years of agriculture almost all our foods, in particular plants, have been purposefully evolved by us. It is quite possible that none of the many recommended diets ranging from vegan to carnivore are ideal for us and that many may even be exposing us to oxidative stress agents that we did not evolve to deal with, which would make glutathione all that more important to our health.
How safe is Glyteine® (GGC) and does it have any side effects?
To test the safety of Glyteine®, an animal study was carried out that involved rats being fed 1 g/kg body weight (equivalent of 100 g for a 100 kg human) of Glyteine® for 90 days with no observed detriment to their physiology.
Will Glyteine® (GGC) effect our health/life span?
Prof Wallace Bridge, UNSW Sydney; explains the greatest benefit of Glyteine® (GGC) is likely to be an improved health span, where we may not necessarily live longer but will stay healthier throughout life*.
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