Hydroxocobalamin and nitric oxide

Discussion in 'Fibromyalgia Main Forum' started by richvank, Jul 9, 2009.

  1. richvank

    richvank New Member

    Hi, all.

    I think many of you are aware of the NO-ONOO theory for CFS that has been developed by Prof. Martin Pall. He and I have been interacting for quite a few years. Below is an email I just sent to him, that might be of interest to people here. Prof. Pall and I have had an ongoing disagreement about the function of hydroxocobalamin in the treatment of CFS. His position has been that it acts as a scavenger for nitric oxide.

    Here's the email:

    Dear Marty,

    In response to your encouragement, I spent most of the day today at the UCSF medical library. I read the references you asked me to read concerning hydroxocobalamin and nitric oxide, cited in your paper, which you sent me. Since the most recent of these references is now ten years old, I also reviewed the more recent literature in this field, since 1999.

    Here’s what I learned: In 2000 a paper was published that showed that previous work in this field had problems with impurity nitrite in the nitric oxide that was used, and as a result, came to incorrect conclusions. At the present time the consensus in the field is that hydroxocobalamin (or aquacobalamin), in which the cobalt ion is in the Co(III) oxidation state, does not react with nitric oxide under physiological pH conditions. However, nitric oxide will oxidize cobalamin from the Co(I) to the Co(II) state, and it will also react with cobalamin that is in the Co(II) state.

    The explanation for the inhibition of methionine synthase by nitric oxide is that during the reaction, the cobalamin coenzyme is reduced from the Co(III) to the Co(I) state, so that nitric oxide is able to oxidize it to Co(II) and then react with it, blocking the coenzyme.

    The explanation for the inhibition of the methylmalonyl-CoA mutase reaction by nitric oxide is that during the reaction, the adenosylcobalamin enzyme is cleaved into cobalamin(II) and a deoxyadenosyl radical. Nitric oxide is able to react with both of them, blocking the coenzyme.

    If you would like to verify this for yourself, I would suggest reading the papers with the following PubMed ID numbers:


    In view of the above-cited developments, I will reiterate my hypothesis that the main action of hydroxocobalamin in the treatment of CFS (together with FolaPro) is to support methionine synthase, thus working to lift a partial block in the methylation cycle. Its action is not to serve as a scavenger of nitric oxide, which it has been shown not to do. A second action of hydroxocobalamin in treating CFS is to support the methylmalonyl-CoA mutase reaction, converting methylmalonyl-CoA into succinate, to supply fuel to the Krebs cycle. It is true that nitric oxide inhibits both these reactions by disabling their respective cobalamin coenzyme molecules, but there is no direct reaction between hydroxocobalamin and nitric oxide.

    Best regards,

  2. heapsreal

    heapsreal New Member

    Just sent a post through about nitric oxide. Whats your opinion on Jay goldstein using viagra for cfs, his reasoning was that it increases nitric oxide and this some how improve symptoms of cfs as well as immune function. I know its a strange drug to talk about with cfs but dr goldstein had some good success with his patients and his understand of brain chemistry.
  3. heapsreal

    heapsreal New Member

    The info i found below shows how its a balancing act of too much nitric oxide harms brain cells.The right amount is usful for the immune system.

    Nitric oxide produced in the brain by the neuronal form of the nitric oxide synthase acts as a chemical messenger at the synapses. The in-vitro and animal experiments showing the role of neuronal nitric oxide in memory has opened a new approach to studies of Alzheimers, Parkinsons and other neurological disorders.

    Too much nitric oxide, on the other hand, may be responsible for killing brain cells in conditions such as stroke.

    In yet another role, nitric oxide helps the immune system's macrophages, the cells in the body that are activated in injury and illness to get rid of debris, when they seek out invading bacteria or cancer cells to destroy. As the "bin men" of the immune system, the macrophages use the cytotoxic properties of nitric oxide to sweep up parasites, bacteria and other potentially infectious rubbish.

    Eddy Liew's work on the role of nitric oxide in the immune system shows the molecule will destroy many organisms that are difficult to kill by other means. And his group has demonstrated the susceptibility to nitric oxide of the vicious parasite that causes Leishmaniasis, a group of potentially fatal tropical diseases caused by parasites transmitted by the bite of sandflies.

    Treatment with the inhibitor L-NMMA also appears to block inflammation in the body associated with the development of arthritis and kidney disease. Moreover, mice genetically engineered not to generate nitric oxide during the immune responses display a reduced inflammatory response. If research now underway confirms the scientists' hypotheses, the advances could lead rapidly to a new class of drugs to control inflammatory diseases that are classified as auto-immune diseases because the affected tissue is under continual attack by its own immune system.

    Research on nitric oxide, its physiological and pathological roles and clinical potential is currently one of the most exciting sources of knowledge in biology.

    The whole article found here, http://www.absw.org.uk/Briefings/Nitric%20oxide.htm

    As well as dr goldstein using viagra to increase nitric oxide he also used small doses on glyceral trinitrate aka anginine, a medication used for angina which has vasodilatory effects which reduces cardiac preload and after load which helps coronary perfusion. Off the top of my head viagra would last longer then anginine.

    You may have written this before but is there an easy way to measure nitric oxide levels, or just a trial and error thing a dr jay goldstein used. Would just have to watch for the headaches if using this stuff.