Snapshot Issue 46 August 2008

L-gulonolactone oxidase

We are all used to being served a glass of orange or grapefruit juice for breakfast. Not so long ago, there was only toast and a cup of tea. When did the orange juice come in? In 1747, a ship’s astute doctor gave oranges to its sailors and, in time, noticed that those that had been suffering from scurvy got better. Today, we know that scurvy is caused by vitamin C insufficiency. The daily dose we require equals to two oranges. Why? Vitamin C takes part in a number of essential functions in our body such as the prevention of aging and the synthesis of collagen which, amongst other things, maintains tissue structure.

Topping up our diets with food items rich in vitamin C seems quite natural to us. However, most mammals make their own vitamin C. So why have humans lost the faculty to do so? It’s all because of Gulo. Gulo is a protein which synthesizes vitamin C. About 40 million years ago, a mutation on the Gulo gene in humans turned out to be fatal and we haven’t been able to produce any since. Gulo is also inactive in other species such as chimpanzees, Guinea pigs and a few bats who, like us, have to find their vitamin C in what they eat.

The metabolic process which results in vitamin C synthesis is complex. A number of bioinformatics tools – known as metabolic maps – are able to render a global and comprehensive visualization of the different stages of vitamin C production. Comparisons between species are then possible and can shed light on differences such as those which exist between mice and men for example.

Hence our incapacity to synthesize vitamin C is the doings of only one protein… Fascinating in a way, isn’t it? And there are many more fascinating tales of the like which revolve around the planet of genes and proteins. Because of – or thanks to – them we are born either male or female. It is also thanks to our genes and proteins that we have the faculty to speak, that we know who our ancestors were and why we feel hungry or replete. And none of this could be at the stage it is now without the help of tools that have developed over the years at the same time as computers evolved – this is the world of bioinformatics.

On the occasion of the Swiss Institute of Bioinformatics’ 10th anniversary, we conceived and created an exhibition ‘Chromosome Walk, a saunter along the human genome’. It was an ideal opportunity to present the tiny world of genes and proteins, which makes us what we are. The exhibition leads you into the heart of a cell and its chromosomes. You are invited to take a walk along our genome and in so doing discover some of the mechanisms that lie beneath the making of Life.

An excerpt from our exhibition, which presents chromosome 8, “How about an orange?”
More on our exhibition here (in french): Chromosome Walk, a saunter along the human genome

L-gulonolactone oxidase (Gulo), Mus musculus (Mouse): P58710

L'édition française de cette chronique est disponible dans l'Instantanés du mois de Prolune.

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Hello Vivienne, with interest I read your article on Gulonolactone oxidase from 2008.

The logical question that comes to mind is whether it could be possible to repair this inborn mechanism of synthesizing vitamin C by administering the missing enzyme. This actually has been done over 20 years ago by mr. Sato and miss Hadley and it has been successful in repairing the ability to synthesize vitamin C in the animal that previously was unable to produce its own ascorbic acid.

So logically one would expect the research to go further and look at the possibility that this repair could be accomplished for humans as well. Unfortunately this has not been done so far. It does not seem that mr. Sato or miss Hadley continued research with L-gulonolactone oxidase, other than to report creation of a polyethylene glycol-linked form for IV injection This probably is the form in which it has to be injected, in order to restore the faculty of synthesizing ascorbic acid.

The principle is rather simple and straightforward, therefor all the more seducing to find out if this would work for humans as well. Specifically people with chronic disease could benefit from such a regained inner production of ascorbic acid.

So my question to you is whether you are aware of research in this direction or know an institute where such research could be done?
With the injectable material already described and probably available, it seems an important and desirable step to take.

Considering the popularity of high dose vitamin C in the battle against so many chronic ailments, it is likely that with the right information, it should be possible to find enough people with the right profile to act as “guinea pigs” in such a study.

The principle of enzyme replacement therapy is already well established and well accepted. (Like in Pompe disease) To do such a replacement with gulonolactone oxidase is therefor not a far fetched idea and I hope you will find it in your heart and mind to give these thoughts some attention.

Posted by Leonard van der Poort on Tuesday 14 February 2012 10:34 CET

I am very interested in knowing if there is anyone who is working on therapy to restore the production of L-gulonolactone oxidase in humans.

Posted by Ralph Gordon on Saturday 2 March 2013 18:54 CET

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