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| Introduction & Bottom Line: | Glutathione has come to the fore recently,
not because it is good stuff, which it is, but because someone found another way
to make a buck off another one of mother nature's molecules. Products are
being hyped with all kinds of immunological razzmatazz. This particular one,
related to glutathione, is simply a high-priced source of cysteine. Some basic
advice. 1. A deficiency of cysteine will hamper glutathione production. Want to hedge your bets? Don't buy the hyped junk; take 100-500 mg/day cysteine. It's considered a limiting amino acid anyway, and could be useful, esp. for vegetarians. 2. Never buy glutathione itself! It's digested! Now for the gory details. |
The Laws of Nutrition: 1. Supplements "cure" symptons and disease to the extent that one is deficient in the nutrient. 2. Amounts of nutrients for "Optimal Nutrition" exist, but are difficult to determine. 3. Pharmacological doses of nutrients generally don't work the way you think they will, and often they work as you hope they would not! 4. Megadoses (officially 10x the RDA) of vitamins (not minerals) are most often not pharmacologic. Megadoses of minerals are bad. |
| About glutathione itself. | Glutathione, although critical in metabolism, is "merely" a peptide of three common amino acids, glycine, glutamate, and cysteine. One of them is connected in a nonstandard way, but is still digestible, therefore pointless to consume. There is probably very little floating around in blood. As you will see, glutathione is a type of anti-oxidant, but better known as a reducing agent. |
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| New Immune enhancing product | This new "immune-enhancing" product is a milk or
soy whey fraction (the soluble protein) which happens to be about 2% cysteine by
dry protein weight, which is in fact pretty high! So it is no doubt good for
you, especially since cysteine is considered an essential and limiting amino
acid in many cases. Methionine, not cysteine, is actually essential, but most
nutritionists lump the two together, for good reason: a large part of the reason
for methionine is to produce cysteine, so we say that cysteine is "methionine
sparing" and therefore quasi-essential. But, if all you are concerned
about is glutathione, rather than paying the BIG BUCKS for these various
isolates, pay pennies for a few milligrams of powdered cysteine. End of this
part of the story. No surprise that these people hawking this stuff don't tell you this. Next you will be hearing that their cysteine is better than my cysteine. Ahh, the segue: |
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| Cysteine vs. cystine. | Cystine is two cysteines joined sulfur to sulfur, the
ubiquitous disulfide bond. The shorthand for cysteine is RSH, where R is the
rest of a molecule, S is sulfur, and H is hydrogen. CystINE is denoted, then,
RS-SR. Cysteine would be considered the reduced form, cystine the oxidized form.
Similarly, reduced glutathione is denoted GSH, where G is the tripeptide, while
GS-SG is the oxidized form. Glutathione, with no adjective, can be either
oxidized or reduced, as they are interconvertible. Frying eggs, perming hair, and digesting food all has to do with the disruption and/or reforming of disulfide bonds. Disulfide bonds "give" protein much of its overall (tertiary and quaternary) structure. More importantly here, cysteine and cystine ALWAYS coexist in some ratio dictated by the equilibrium constant K for this compound: 4RSH + O2------> 2RSSH + 2H2O, where oxygen, the oxidizer, has been reduced by the H's of cysteine, forming cystine as the product. This reaction, however, is not likely to be quick, and if cysteine is ingested, it is likely to stay as mostly cysteine, IMO. EVENTUALLY, cysteine in solution will convert to cystine because of oxidation by dissolved oxygen. But I do not believe cysteine in the blood hangs around long enough for this to be appreciable. But bear in mind that there is always some mixture. |
A reducing agent is basically an anti-oxidant. |
| Should you take cystINE? | No. If you did, the stomach and intestine, being the
destroyer of all that is disulfide, would form cysteine anyway. Think about it:
You are eating great amounts of intact protein, replete with the S-S bonds that
hold it together, yet you absorb free amino acids. Research has been cited that stated some cells require cystINE for their glutathione production. First, I don't believe it. Second, if it's true, there is nothing you can do about it dietarily. Third, if it is true that cysteine is oxidized in the blood to form cystine, cells that take up cystine probably do so as a method for clearing it. Just guessing, however. |
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| Oxidation & reduction: Can Glutathione do this by itself? | O2 (molecular oxygen) is the classical oxidizer, and H (or H2, molecular hydrogen) is the classical reducing agent. When the twain meet, BANG, you get water. Recall the Hindenberg: Fire and rain, simultaneously! No kidding! Similarly, when cysteine meets O2, you get the reaction cited previously. Ditto glutathione, in an exactly analogous equation. But can glutathione run around and reduce everything it touches? Well, some things. But for most things it needs an enzyme (eg, glutathione peroxidase). Can RSSR or GSSG oxidize everything they touch? Generally not. GSSG requires glutathione reductase to regenerate GSH. An interesting question is, if GSH can reduce other disulfide bonds, can RSH (cysteine) do the same? Don't know, but probably not. Interestingly, one of the primary functions of glutathione is in the enzymatic de-activation of peroxides. This is interesting because at first glance, it would appear GSH should be able to do this all by itself without an enzyme, given the reactivity of peroxides. But, fooled again, it cannot. |
Vitamin C as an antioxidant (reducing agent) Vit C is used industrially as a preservative and antioxidant, particularly in bacon for the prevention of nitrosamines. Like glutathione, it too can act with and without enzymes as a reducing agent. Interestingly, Vit C is used as an enzyme cofactor in oxidizing cholesterol to bile. No C, high cholesterol!! |
| How Glutathione is made; Does extra cysteine mean extra glutathione?? | Glutathione production is part of a
well-known cycle designed for amino acid transport, across cellular membranes,
the cellular equivalent to ingestion. Amino acids, being charged, cannot pass
through the lipid bilayer by themselves. Glutathione itself is shuttled back and
forth across the membrane to carry these incoming amino acids. Within this
cycle is the provision for making glutathione itself. What happens to "extra" cysteine imported into these cells? Do they induce extra glutathione? Very hard to say for sure, but, given the number of enzymes involved in this whole cycle, it is possible, but NOT likely. It totally depends on the substrate requirements for the enzymes. You can bring water to an enzyme, but you can't always make it drink! It is especially difficult to say here, as glutathione is doing such a double duty. And who is to say that cysteine is even going to get IN the cell via this transport mechanism? If cysteine is not selectively transported in (but it might be), there is little reason to expect that high blood levels of cysteine, or any other amino acid, will be transported in, if the transporting enzyme is otherwise regulated (and they usually are!). |
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| What biochemists do about glutathione? | Which is why, upon getting all this junk email or glowing reports of X, Y Z doing ABC, biochemists don't run out right away and BUY stuff. You could have a ton of glutathione, but if you don't have the enzymes, what good is it? Similarly, just because you have a lot of cysteine does not mean a lot of glutathione will be MADE! There are AT LEAST half a dozen enzymes that must coordinate before cysteine winds up as a USABLE glutathione SYSTEM. | |
| Conclusions--sort of | So what happens with all the extra cysteine one takes? I
don't know. And I doubt anyone else does. It is not an easy thing to show,
that extra cysteine gives you extra reducing power in the glutathione system.
It certainly could, but it probably has much less than a 50/50 shot. If enzymes were NOT involved, then it would be necessarily true that more cysteine would give more glutathione (Le Chatelier's principle, and all that). But not with enzymes. It could ALSO be the case that with a little bit of cysteine, BANG, every molecule is converted to glutathione. That is another possibility, and in fact some enzymes are designed to be that "complete," if you will. But it's a tough call. The intelligent thing to do is make sure you do have enough cysteine. You at least want to make sure that a simple substance is not bottlenecking the whole operation. Bear in mind that methionine produces cysteine in the body, but that dietary cysteine lightens the metabolic load on methionine. But it is also possible for too much cysteine to affect methionine's other functions through feedback inhibition, etc. My solution? No more than 500 mg supplemental cysteine, if glutathione is your concern. A little supplemental cysteine is not a bad idea, esp. for vegetarians. |
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| The other component of glutathione: Glutamate or Glutamine? Other topics on Protein |
Well, what about Shabert and his "Ultimate Nutrient:
Glutamine". Well, dollars to donuts Shabert does not take extra
glutamine. Glutamine and glutamate are essentially interchangeable, as far as the body goes. If you have one, you for SURE have the other, via very short amination/deamination pathways. GlutamATE is in fact the "sponge" for the chronic ammonia in the body, and too much glutamine COULD interfere with glutamATE being converted to glutamINE (the "soaked sponge" form of glutamate). This is probably not a big deal even for fair sized doses of dietary glutamine, but why make the body struggle? It would seem that metabolism of excess protein is THE major source of toxin, ammonia, in the body, which is nevertheless well equipped to handle it. But also realize that forcing the body to degrade even just a few grams of extra protein is probably the ammonia equivalent of ALL OTHER NITROGEN METABOLISM COMBINED!! IOW, protein is a messy way to get energy. In fact, a priori, I would have guessed that protein was not at all intended to be used as fuel. Exclusive carnivores however, shoot that theory down. And the question is, Where does man fit in this scheme? It remains to be seen what our ancestors really did eat. Assuming it was blood red meat, it remains to be seen if that indeed is an optimal diet. Regarding natural, remember, nuclear energy is natural. And, we get way above the RDA for protein anyway, so it would seem silly to supplement anything beyond the limiting essential amino acids, typically methionine/cysteine, lysine, and tryptophane. And then at less than 500 mg amounts. |
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