Hi, I looked at ways to improve hypoxia tolerance back in the late 90s. I think two aminos stood out, glycine and alanine. At the time no mechanism was known, at least to me, as to why this helped. It was just an empirical observation with hypoxia researchers. This all ties in with H2S and NO of course, its all connected. Unravelling the connections is the trick - they exist but are they relevant in all ME patients, just a subset, or none? It just begs for more research. So much of our hypothetical biochemistry is like that: this is real chemistry, but is it relevant? My mantra has always been: we need more research.
One critical factor, again empirical, that I was very interested in, was that massive amounts of arachidonic acid are released during reperfusion injury events. Arachidonate stimulates a massive oxidative stress burst from the mitochondria (mechanism unknown in 2000 or so). It also induces inflammatory hormone synthesis, way too much. This mechanism is probably why alchohol poisoning kills, as arachidonate is released at high alcohol concentrations (biologically high, as in very drunk). When this is blocked with drugs, alcohol poisoning becomes nonfatal.
Bye
Alex
Hi Alex,
I do believe in the underlying hypoxia/oxidative stress theories of ME/CFS, (which is not to say oxygen is toxic), and I think that H2S may go a long way toward explaining these findings. As for oxygen, rather than it being toxic, it may be a big part of the solution.
What I like about your comments is that you assume that ME/CFS is related to the gases, which is not a commonly held view! In fact, it is a pretty radical view, but one which, I think, eventually, will come to be accepted. It is my hypothesis that disturbances in H2S metabolism and homeostasis are the key to this disease. Life began with H2S, and there is a reason why H2S has been conserved in our mitochondria as a substrate alternative to oxygen since then. Emerging research on redox will eventually bear this out, I think, but we shall see.
Regarding arachidonic acid, I have always wondered about this, and yes, H2S plays a role, which tells us something about its effect on fatty acid metabolism, another problem evident in PWC. In the reperfusion/arachidonic cascade process, a recent study suggests that H(2)S could activate PLA(2), which in turn releases arachidonic acid leading, initially, to vasoconstriction followed by vasodilation mediated by cytochrome P450-derived metabolites.:
http://www.ncbi.nlm.nih.gov/pubmed/21228064 The study goes on to say that H2S may act through the Endothelium-Derived Hyperpolarizing Factor (EDHF), which is involved in the hyperpolarization and relaxation of vascular smooth muscle cells.
Another article (
http://www.ncbi.nlm.nih.gov/pubmed/21980127) confirms this finding and explains how it works: H(2)S is a major EDHF that causes vascular endothelial and smooth muscle cell hyperpolarization and vasorelaxation
by activating the ATP-sensitive, intermediate conductance and small conductance potassium channels through cysteine S-sulfhydration. It goes on to say Because EDHF activity is a principal determinant of vasorelaxation in numerous vascular beds, drugs influencing H(2)S biosynthesis offer therapeutic potential. I second that idea!
BTW, it is also of note that that EDHF plays a key role in celiac disease:
http://www.celiac.com/articles/2252...al-Inflammation-in-Celiac-Patients/Page1.html. This should not pass unnoticed!
As for specific amino acids, that is a very complex subject. Does an excellent profile and analysis of ME/CFS amino acids patterns exist anywhere? That would be useful. I believe cysteine deserves far more attention, read NAC and P-5-P.
Just to bring this discussion full-circle, EDHF is involved in cAMP (a few posts back).
http://www.pnas.org/content/99/9/6392.full
From the few posts Ive made, I think it is obvious that there are many, many reasons to look seriously at hydrogen sulfide metabolism and its role in ME/CFS. I'd like to hear more about blocking arachidonic acid.
All best,
Marian
