Before I read this article and looked some of the articles related to it and cited in it, I had read about ribose a few years ago and hadn't thought much of it. I've also across a lot about it in relation to nucleotide metabolism in the context of ischemia and in the neuroprotective effects of nucleotides. This is a great article:
http://www.ncbi.nlm.nih.gov/pubmed/3102830?dopt=Abstract
What's interesting is that ribose does not have anywhere near this kind of effect on endurance exercise in normal people, and the exercise side of it is not what interests me. The authors of that article and the related ones talk about the way they don't think ribose works in "myoadenylate deaminase deficiency" (heterogeneous as that group of disorders is) by increasing the activity of the purine nucleotide cycle in skeletal muscle cells. They also say that they don't think it works by being used as "fuel" per se, but the hypoglycemic effect of it implies that there's some effect, as they say, of activating glycolysis and initiating some kind of cyclic process that allows the utilization of carbohydrates, from the blood, etc., to be increased in people with this low activity of myoadenylate deaminase. It's possible that low myoadenylate deaminase activity is some generic marker for acquired myopathies and that there are other metabolic abnormalities in the people's muscles. I find it hard to believe that all of these people, with diverse "causes" of this myopathy, would develop a completely selective deficiency in the activity of only myoadenylate deaminase. But it doesn't even matter, really, because the authors don't think that ribose is specifically and selectively enhancing the activity of this enzyme. It's allowing some process to occur that's bypassing the deficit in the activity of the enzyme. This could be relevant for the neuroprotective effects of nucleotide-derived ribose-1-phosphate, which is converted into ribose-5-phosphate (as ribose is) and then enters the nonoxidative pentose cycle, among other metabolic fates.
Another thing that's interesting is that the authors of that article found xylitol to be equally useful but to have significantly different, and fructose-like, effects on purine nucleotide export from the skeletal muscles during exercise. Fructose and xylitol both cause this elevation of uric acid, acutely, but ribose doesn't cause nearly as much of this. There's some of it, but not nearly as much as with xylitol, apparently. That's strange, because a lot of xylitol is supposedly converted into ribose-5-phosphate, after a two-step conversion. Here's one interesting, possible explanation for the effects of ribose in skeletal muscle (an "alternative" scenario involving the pentose cycle). I'll probably post more about this as I learn more about it. That first article also talks about the safety issues and blood levels, and there may be some antiproliferative or apoptotic effect on lymphocytes at very high doses (as in one study showing a trend toward a lower WBC count at 20 g/d of ribose). That would be a very and unnecessarily high dose, however. And the concentrations that produced those antiproliferative effects in vitro were in the range of 20-50 mM of extracellular ribose in the culture medium, and the serum ribose only reached a maximum of 3.4 mM in humans with myoadenylate deaminase deficiency who received the infusions of ribose. The 50 mM levels used in those in vitro studies are obviously supraphysiological, but ribose does seem to have a surprisingly long "half-life," if one can call it that. There was apparently not a steady-state effect, in terms of the hypoglycemic effects, after 14 days. I forget if it's 4 or 5 half-lives that are required to reach a steady-state, usually, from a pharmacological standpoint, but, in either case, this would imply that the "half-life" of the effects of ribose could be longer than 2 or 3 days. The hypoglycemic effect does seem to be pronounced at doses in the range of 20 g/d, too, and that seems to be a bit much. There's a study showing the hypoglycemic effect doesn't really emerge as much at doses below 10 g/d. I don't have a good enough understanding of the reasons underlying the hypoglycemia to tell how this would interact with nucleotide metabolism in the context of neurodegenerative diseases, but I'll probably wind up reading more about it. Here's the article on the "alternative" cycle that ribose-5-phosphate may contribute to:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1166176
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