Ascorbic Acid

``Free oxygen, 0₂, is a strong electron acceptor and so its appearance in the $\beta$ period opened the way to a higher degree of electronic desaturation, and to the corresponding higher degree of differentiation and development. If nature develops a new method, as a rule, she does not throw the old one out, but simply adds the new one to it, improving it. So, in the $\beta$ period, methylglyoxal was not replaced by 0₂, but the 0₂ was added to it, boosting up its acceptor strength.

However, oxygen does not interact with protein, nor does it interact with methylglyoxal. So in order for it to be used as an acceptor for protein, a link had to be developed by which the oxygen could be linked to methylglyoxal, transferring to it part of its acceptor power. This link had to have very specific qualities: it had to be able to make a bond simultaneously both with oxygen and methylglyoxal and had to have an electronic mobility by which it could transfer the acceptor strength of 0₂ to the ketoaldehyde. This new substance, which nature developed when light and oxygen appeared, is ascorbic acid, discovered by me in the early thirties. Later it was found to have an antiscorbutic activity, and to be identical with the then unknown antiscorbutic component of fresh vegetables called ‘Vitamin C’.

In a remarkably short time the chemical nature of ascorbic acid was cleared up and the substance became available at low cost in crystalline condition in an unlimited quantity. But while we have learned everything worth knowing about its chemistry, its biological function remained unknown, preventing medicine from making full use of its remarkable reactivity. We can control only what we understand. Even a simple question, such as the magnitude of the recommended daily dose, has remained unsettled, oscillating between megadoses and a few milligrams.

The development of ascorbic acid is one of the landmarks of evolution, as was the appearance of light and oxygen. That ascorbic acid readily interacts with oxygen can be shown by placing a sample of its Na salt into the e.s.r. spectrometer in the absence of oxygen. On admission of air the typical free radical signal appears, consisting of a doublet with a splitting of 1.75 gauss. Each part of the doublet has a further triplet splitting of 0.175 gauss.

That ascorbic acid can readily interact with methylglyoxal has been shown by Fodor, who will describe his observations later in this symposium (Fodor ei at., pp. 165-169).

The great mobility of the unpaired electron inside the ascorbate radical can be demonstrated by e.s.r. which shows that this electron can interact with many of the protons of ascorbate.

Also, the spectrometer gives valuable information about the interaction of oxygen, ascorbate and methylglyoxal, which information has hitherto been utilized only to a small extent. If methylamine and methylglyoxal solutions are mixed a very strong signal appears with a rich hyperfine structure. In the presence of ascorbate the signal is much stronger, showing that the ascorbate catalyses charge transfer, without changing the character. If casein is treated with methylglyoxal in the presence of ascorbate, a new signal appears (P.C.R. Gascoyne, personal communication), indicating that the ascorbate is built into the charge transfer complex-an observation which may have far reaching biological consequences and introduces new viewpoints into the medical use of the acid.

Most fascinating and complex spectroscopic reactions have been found by my colleague Jane McLaughlin (unpublished results). If both cuvettes of the spectrophotometer contained a mixture of a 0.0256M solution of methylglyoxal and methylamine (0.077M), and 0.0077M-ascorbic acid was added, a very strong absorption appeared around 400 nm, which disappeared slowly (Fig. 8). A second peak appeared around 500 nm. In the absence of oxygen the addition of ascorbic acid made no difference, showing that it catalysed the charge transfer between 0₂ and methylglyoxal. If no ascorbate was present, admission of oxygen to the mixture of methylglyoxal and methylamine inhibited the appearance of the absorption spectrum.

Oxygen, essentially, brings the life-giving light into the living system. Ascorbic acid catalyses this reaction. It is involved in bringing matter to life. This opens up new aspects of the medical application of ascorbic acid.

The actual role played by oxygen in these reactions is yet unknown and demands more study on the basic level. It is possible that the 0₂ molecule simply takes an electron over and dissociates off, but it seems more likely to me that it takes over only parts of an electron and remains attached to the charge transfer complex. If, in this ease, the oxygen pressure is decreased, the oxygen may dissociate off, upsetting the electron balance in the whole charge transfer mechanism. This may explain why consciousness instantaneously fades out if the oxygen supply to the brain is cut off. This suggests also that in the comatose state after a heart attack the infusion of ascorbic acid and artificial respiration might be indicated.

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Taken from Szent-Györgyi.

Amazing man. I knew about Linus Pauling, but not about this scientist; I guess they were friends. Yes they were ``The Healing Factor.''