Sunday, January 14, 2018

Molybdenum for Gastroenteritis Nausea and Vomiting, part 2

(continued from the previous post)

Gastrointestinal infections, Hydrogen Sulfide, and Sulfite 

A typical part of a viral gastroenteritis infection is damage to the mucosa (lining) of the proximal small intestine (the part of the small intestine closest to the stomach).[1] Our bodies make and use hydrogen sulfide (H2S) while working to protect the gastric[2] [3] and intestinal mucosa.[4]

It is still being investigated exactly how H2S is afterward transformed in the body, but one of its catabolic products is known to be sulfite. Moreover, it was recently discovered that there appears to be a previously-unknown H2S oxidation pathway using neuroglobin.[5] Neuroglobin has been discovered to be expressed in the cells of the stomach fundus and the small intestine after hypoxia.[6] I suspect that neuroglobin-assisted H2S catabolism results in more net sulfite than the better known sulfide:quinone oxidoreductase catabolic pathway and that it could be a major contributor to the presence of sulfite in the stomach and small intestine at levels high enough to trigger vomiting.

In most people, sulfite oxidase typically seems able to handle the amount of sulfite resulting from endogenous hydrogen sulfide metabolism. However, in the absence of sufficient molybdenum, magnesium,[7] or P5P (active vitamin B6 is involved in making heme, which is part of sulfite oxidase),[8] sulfite oxidase might not reach necessary levels of activity, for those three nutrients are needed to form sulfite oxidase and the molybdenum cofactor. The main result of insufficient sulfite oxidase activity is a buildup of nausea-inducing sulfite. It thus follows that supplemental molybdenum can reduce nausea.

mARC 1 and mARC 2

Two relatively recently discovered molybdenum-utilizing enzymes are the mARC 1 and mARC 2 enzymes. They appear to be involved with nitric oxide (NO) production,[9] and NO and H2S cooperatively interact in many ways.[10] [11] Thus mARC1 and mARC2 might also be involved in the pathophysiology of nausea and vomiting.

Conclusion

I have written this because I have seen molybdenum dramatically prevent nausea and vomiting from gastrointestinal viruses, as well as shorten the duration of gastrointestinal virus symptoms even after vomiting has already begun. I think current research supports a hypothesis that molybdenum does so by supporting optimal activity of the molybdenum-utilizing enzymes sulfite oxidase and possibly mARC1 and mARC2.

Because this discovery has great potential for improvement of public health, I think it urgent for professional researchers to explore molybdenum’s effect in alleviating gastrointestinal virus-caused nausea and vomiting and establish appropriate dosage guidelines for its use.

- CT

References



[1] Widerlite L, Trier JS, Blacklow NR, Schreiber DS. Structure of the gastric mucosa in acute infectious bacterial gastroenteritis. Gastroenterology 1975;68(3):425-430.
[2] Bronowicka-Adamska P, Wróbel M, Magierowski M, Magierowska K, Kwiecień S, Brzozowski T. Hydrogen sulphide production in healthy and ulcerated gastric mucosa of rats. Molecules 2017;22(4). pii: E530.
[3] Souza LK, Araújo TS, Sousa NA, Sousa FB, Nogueira KM, Nicolau LA, Medeiros JV. Evidence that d-cysteine protects mice from gastric damage via hydrogen sulfide produced by d-amino acid oxidase. Nitric Oxide 2017;64:1-6.
[4] Wallace JL, Caliendo G, Santagada V, Cirino G, Fiorucci S. Gastrointestinal safety and anti-inflammatory effects of a hydrogen sulfide-releasing diclofenac derivative in the rat. Gastroenterology 2007;132(1):261-271.
[5] Bilska-Wilkosz A, Iciek M, Górny M, Kowalczyk-Pachel D. The Role of Hemoproteins: Hemoglobin, Myoglobin and Neuroglobin in Endogenous Thiosulfate Production Processes. Int J Mol Sci 2017;18(6). pii: E1315. doi: 10.3390/ijms18061315.
[6] Emara M, Turner AR, Allalunis-Turner J. Hypoxic regulation of cytoglobin and neuroglobin expression in human normal and tumor tissues. Cancer Cell Int 2010;10:33.
[7] Mendel RR. The Molybdenum Cofactor. J Bio Chem 2013;288:13165-13172.
[8] Heinemann IU, Jahn M, Jahn D. Arch. The biochemistry of heme biosynthesis. Biochem Biophys 2008;474(2):238-251.
[9] Sparacino-Watkins CE, Tejero J, Sun B, Gauthier MC, Thomas J, Ragireddy V, Merchant BA, Wang J, Azarov I, Basu P, Gladwin MT. Nitrite reductase and nitric-oxide synthase activity of the mitochondrial molybdopterin enzymes mARC1 and mARC2. J Biol Chem 2014; 289(15):10345-10358.
[10] Farrugia G, Szurszewski JH. Carbon Monoxide, Hydrogen Sulfide, and Nitric Oxide as Signaling Molecules in the Gastrointestinal Tract. Gastroenterology 2014;147(2): 303–313.
[11] Szabo C. Hydrogen sulfide, an enhancer of vascular nitric oxide signaling: mechanisms and implications. Am J Physiol Cell Physiol 2017 Jan 1;312(1):C3-C15.

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