The Cell Kingdom

In the land of human systems, in the time of anti-oxidation, the destiny of a kingdom lies on the shoulder of a clan, this clan is called the GLUTATHIONE!

If you did not read the sentence above in the voice of the Great Dragon of the movie Merlin, please kindly go back and do that now. Thank you!

There was peace in the land for twenty years. For twenty years criminal illegal immigrants and outlaws were kept out of the kingdom, and if at all they gain entrance, they are immediately dealt with by any of the successors of a great warrior named Glutathione.

But then, those good years were soon out of sight, the Glutathione clan began to decrease in number and therefore collective strength. The kingdom began to experience series of attacks from outlaws and inner foes, bringing dark days upon the Land and gloomy days upon the Kingdom. All attempts, all efforts, and every single trial towards alleviating these problems were unsuccessful.

Days became weeks, and weeks to months, then years, the household of Glutathione, a prominent defender of the Kingdom continued to decrease by their numbers. Nature had refused to add to them. This is so because they do not give birth to offspring as they are not entirely humans but depend on Mother Nature to orchestrate the coming together of THREE PARTS of a mystical compass.

Before we get back to our story, let me tell you some necessary things about the Glutathione clan

Since the very beginning of the existence of Kingdom Cell, the founders of this great Kingdom discovered three magical compasses scattered in different positions not more than a hundred centimeter (100 cm) from each other. Curious about what they were and their usefulness, the founders got the three pieces and tried for days to decipher what they were meant for.

Alas on a faithful day, Lord Neo the great (one of them founders) mistakenly joined correctly the pieces and suddenly the sky became all white and a man jumped out of the now rightly aligned compass. This returned the compass to its initial state, separated into the three pieces and scattered in same distance and location.

The compass man (formed from the perfectly fitted compass parts) was in all fighting skills perfect, he feared no one and was way stronger and mightier than Samson of the Hebrew stories. He protected the land from both inward and external attacks. These attributes got him the name “Glutathione”.

At every full moon, a gentle breeze brings the scattered compass parts together and each time this happens, another Glutathione is birthed. That was how the Glutathione clan grew bigger and stronger defending the kingdom.

Now back to after twenty years

The kingdom had been so dependent on the Glutathione clan, they never expected to experience a decline in their population as a result of the compass parts refusing to come together. After proper investigation was conducted, it was identified that one of the compass parts was missing and they had to wait until Nature brings this missing part from God knows where.

The problems encountered by Kingdom Cell had serious adverse consequence on the peace of the entire country as Cell largely determines what happens in the country as a whole.

The clan is an antioxidant called glutathione, the kingdom is a typical human cell and the country is the entire human system. The three essential compass parts that makes up a glutathione man are L-Cysteine, L-Glutamic acid, and Glycine. The missing part of the compass from the story which needed supplementation from external source is the amino acid L-Cysteine.

The defense system powered by glutathione and many of its functions we will discuss some in this article. The problems experienced by the kingdom above could be summarized as oxidative stresses. While those experienced by the country range from conditions like Hypertension to cancer and many other disease states.

In few paragraphs, we will open up this antioxidant, its importance and functions, problems from decreased quantity in the cell (how it arose, and the consequences), what happens beyond age twenty. Sit tight, let’s ride together.

Definition and Structure of Glutathione

There are virtually no living organisms on this planet be it animal or plant whose cells do not contain some glutathione ^source

Glutathione (C₁₀H₁₇N₃O₆S) is an antioxidant secreted by cells of humans, animals, plants and even microorganisms.

Glutathione is a Tripeptide ^source
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Being an antioxidant, it inhibits certain reactions orchestrated by reactive oxygen species such as free radicals, peroxides, lipid peroxides, and heavy metals ^source. These reactions (mainly oxidations) are capable of causing damage to important cellular components ^source.

A molecule of glutathione is a tri-peptide, that is, it is made up of three amino acids L-Cysteine, L-Glutamic acid, and Glycine. It is constructed by a gamma peptide linkage and a normal peptide bond between the carboxyl group of glutamate and the amino group of cysteine, and between the carboxyl group of cysteine and amino group of glycine respectively.

One important member of the three amino acids gang that make up glutathione is cysteine as it carries the thiol ( –SH) group that confers antioxidant capabilities upon the parent structure (glutathione) ^source.

Glutathione Synthesis

from this junction, you will be seeing more of biochemical terms, don’t get misplaced and don’t get bored

With two ATP (Adenosine Triphosphate) dependent steps, glutathione is synthesized in our cells. There is no need for it to be supplemented in our diet and hence, it’s not an essential nutrient. These two steps involve at first, the action of gamma-glutamylcysteine synthetase also called glutamate cysteine ligase (GCL) coordinating a merge between L-glutamic acid and cysteine to form gamma-glutamylcysteine. Glycine is then added to the C-terminal of gamma-glutamylcysteine to form a complete molecule of glutathione via the action of the enzyme glutathione synthetase.

As if we have seen above that cysteine is the link between glutamate and glycine, and the fact that it is the contributor of what makes glutathione an antioxidant, we may therefore say a reduction in the bioavailability of cysteine in cells which also means the formation of gamma-glutamlcysteine can be a rate-limiting step in glutathione synthesis.

How Essential is Glutathione?

Oxidative stress a summary of the problems suffered by the kingdom in our illustration at the beginning of this article, was defined by Mehta et al. (2007) as "An excessive generation of reactive oxygen species (ROS), such as superoxide (O₂^-) and hydrogen peroxide (H₂O₂), beyond the body’s innate ability to counter their noxious effects" ^source.

Preventing oxidative stress is a major function of glutathione

Thiol (-SH) group on glutathione carries a hydrogen atom (H-atom) which can be donated as a reducing equivalent (an equivalent of one electron) in reactions. Therefore, glutathione molecule may exist in any of two states, reduced (when the H-atom on the –SH group of the cysteine component of glutathione is still intact) or oxidized (when the H-atom has been donated).

Donation of H-atom is made to other molecules, for example, to reactive oxygen species thereby neutralizing them, or to protein cysteines to maintain their reduced forms. By so doing, glutathione itself becomes oxidized, reactive, and readily available. It eventually finds itself another reactive glutathione molecule (this is most probable situation because of the high concentration of glutathione molecules in the cell), the two undergo addition reaction to form glutathione disulphide (GSSG).

Depending on the concentration of reactive oxygen species in the cell, the levels of reduced state of glutathione (which is the antioxidant active state) in the cell may experience a sharp drop. This condition is returned back to balance by the action of the enzyme glutathione reductase which works hand in hand with NADPH (reduced form of Nicotinamide Adenosine DiPhosphate) to split a molecule of GSSG into two molecules of reduced glutathione. The cycle then repeat itself. However when the ratio of GSSG to reduced glutathione is increased to certain levels, the cell is said to be in a condition characterized by oxidative stress.

A cell has lot of haters, these include free radicals, chemical toxins, radiation, and heavy metals. A prominent defender of the cell is glutathione as it is a major first responder to invasion of cells by toxins that come into our body through foods, drugs and water. We know it is the primary function of liver cells to take care of toxins in the body hence, synthesis of glutathione in cells of the liver should never be interrupted.

The same applies to the lungs as their cells utilize glutathione to destroy virtually every toxic air particle that we breathe in before oxygen is delivered for circulation throughout the body. Our brain cells use up about 20% of body oxygen therefore, high level of reactive oxygen species from oxidative metabolisms in brain cells should be expected. Hence, the essentiality of glutathione synthesis and antioxidative function in our brain. ^source.

Glutathione ensures that other antioxidants such as vitamin C and vitamin E are returned back to their reduced form after they have been utilized in the body. That is, it plays major role in the feedback mechanism or recycling of other antioxidants.

It has essential role it plays in metabolic and biochemical reactions including DNA synthesis and repair, protein synthesis, prostaglandin synthesis, amino acid transport, and enzyme activation. Considering these many functions, we can conclude that a problem to glutathione is a problem to the entire human system from immune to nervous and gastrointestinal systems ^source.

Glutathione Benefits^source
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In addition, glutathione supports protein biosynthesis by coordinating inward transport of amino acids into cells. It is also a good supporter of the defense campaign of our immune system. Glutathione has many other important functions as found in many science research articles.

L-Cysteine; A Limiting Factor

Research as it that as humans grow an increase in age, due to our lifestyles, drops in level of L-Cysteine uptake will eventually begin to become more consequential with respect to level of glutathione synthesized in the cell. This so because, prior to adulthood, human cells were able to construct fair quantities of glutathione even with levels of cysteine they were been supplied (that is, quantity of cysteine uptake).

However, as we grow older, say from age twenty, cellular needs for glutathione increases but, production rate does not scale up to meet cellular needs, and as a result, cells yearn for more L-cysteine to make more glutathione molecules ^source.

Glutathione Deficiency Problems

Levels of glutathione may go down beyond what the cell can handle, with respect to what seemed like a continuous stream of attacks by some toxins, heavy metals, radiation and of course free radicals on our cells resulting in depletion of cellular glutathione concentration while increasing the GSSG to reduced glutathione ratio.

Some Conditions Associated with Glutathione Deficiency^source
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This is a single problem however, its effects are seen on virtually every of our tissues and therefore organs and systems are not excluded.

Low cellular glutathione concentrations has been linked with hypertension, heart diseases, stroke, cataract and glaucoma, accelerated aging, increased cellular inflammation, fatigue and disease vulnerability, reduced mental focus and athletic performance, and more weakened immune system among many other conditions.

We need to therefore help our cells out of this situation. One seemingly good way anyone will easily come up with is to take glutathione supplements. However, this approach may not yield desired results in our cells. Reason is, glutathione has no way of getting into our cells, as there are no receptors for the molecule on cellular membranes. Secondly, there are enzymes synthesized in our body called proteases which see molecules of glutathione from supplements as substrates for them to act on. So, a typical glutathione supplement will most likely get digested by proteases in our gut.

Crucial series of research has led to the idea of supplementing our cells with L-cysteine. During twenty-five years or research, Dr Nagasawa discovered that L-cysteine combined with a ribose sugar was the magic bullet needed to supply cells with L-Cysteine, the limiting factor in glutathione biosynthesis^source.

The word “limiting” in this context refer to a condition in which the concentration of one or more of needed micro substance in the synthesis of a larger substance, is not up to the level required to make this larger substance hence, limiting the synthesis of the same. This micro substance is therefore said to be a limiting factor.

How does this ribose cysteine combination work?

D-Ribose and L-Cysteine was combined to form what he (Nagasawa) termed as RiboCeine. The presence of D-Ribose makes cell’s membrane permit entrance of the combo into the cell. This sugar will be used by cells as source of ATP (energy) while, L-Csyteine will be made available to combine with glutamic acid and glycine to form a glutathione molecule ^source.

Apart from this breakthrough technology (RiboCeine), L-Cysteine can be found naturally in meat which includes pork and poultry. Plants rich in L-Cysteine include red peppers, garlic, onions, broccoli, Brussels, sprout, oats, wheat germ, and sprouted lentils^source. Although, the amounts of cysteine we get from these food materials may not supplement enough still, we need to ensure at least one or more of these food materials are part of our daily meals.

CONCLUSION

In summary, we have discussed the striking importance of glutathione in our cells, how it is synthesized, L-Cysteine as a limiting amino acid in glutathione synthesis and how this problem can be alleviated. We saw the many conditions that could arise if we do not make a responsibility of supplementing our body cells with L-Cysteine. And finally, in a short sentence we can agree that cellular glutathione concentration levels determines everything!

Health is wealth, and so are cellular glutathione molecules.

Thanks for reading!!!

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