Tuesday, September 20, 2016

Sulfite oxidase in the stomach and chloride

The pH of the stomach is low, or acidic, ranging from 1-5. This is important because where the pH is less than 7, the enzyme sulfite oxidase is slightly different from high pH sulfite oxidase, i.e., where pH is higher than 9. The low pH form of sulfite oxidase can become blocked when there is not enough chloride. Here is a 2010 research report discussing this:
The Mo(V) state of the molybdoenzyme sulfite oxidase (SO) is paramagnetic and can be studied by electron paramagnetic resonance (EPR) spectroscopy. Vertebrate SO at pH < 7 and pH > 9 exhibits characteristic EPR spectra that correspond to two structurally different forms of the Mo(V) active center referred to as the low-pH (lpH) and high-pH (hpH) forms, respectively. Both EPR forms have an exchangeable equatorial OH ligand, but its orientation in the two forms is different. It has been hypothesized that the formation of the lpH species is dependent upon the presence of chloride. In this work we have prepared and purified samples of wild type and various mutants of human SO that are depleted in chloride. These samples do not exhibit the typical lpH EPR spectrum at low pH, but rather show spectra that are characteristic of the blocked species that contains an exchangeable equatorial sulfate ligand. Addition of chloride to these samples results in the disappearance of the blocked species and the formation of the lpH species. Similarly, if chloride is added before sulfite, the lpH species is formed instead of the blocked one. Qualitatively similar results were observed for samples of sulfite oxidizing enzymes from other organisms that were previously reported to form a blocked species at low pH. However, the depletion of chloride has no effect upon the formation of the hpH species.

Therefore, to have properly functioning sulfite oxidase in the stomach, it seems that we need chloride, or Cl-, there. (Note: this is not the chlorine that you think of as bleach or for use in water disinfection. That chlorine is Cl2.) Fortunately, we usually have plenty of chloride in our stomachs because of the hydrochloric acid (HCl) that is the main acid in our gastric juice. But during pregnancy we don't have enough hydrochloric acid in our stomachs. Per this study from 1936, almost no pregnant woman has normal levels of hydrochloric acid in her stomach by the end of pregnancy:

Gastric analyses.-Analyses were made upon 115 cases, 60 ante- and 55 post-partum. In the first trimester, 51 per cent of the cases showed normal gastric acidity; 40 per cent had hypochlorhydria, and 9 per cent achloryhdria. In the second trimester, 13 per cent showed hypochlorhydria and 87 per cent showed achlorhydria; in the third trimester, 0.5 per cent showed normal acidity, 3.5 per cent hypochlorhydria, and 96 per cent achlorhydria. 


Hypochlorhydria is low hydrochloric acid in gastric secretions; achlorhydria is the absence of hydrochloric acid in gastric secretions. Hypochlorhydria was found to be significantly associated with dyspepsia (i.e., heartburn, nausea, belching, upper abdominal pain) in females per a 2013 study (https://www.ncbi.nlm.nih.gov/pubmed/22829345). This gestational lack of hydrochloric acid fits well with the very common (up to 80%, per https://www.ncbi.nlm.nih.gov/pubmed/18843742) experience of heartburn during the third trimester of pregnancy.

But back to sulfite oxidase. As discussed many times previously, we want it functioning properly to break down sulfite in the stomach and upper intestine. So we need chloride in the stomach. If the gastric secretions don't include enough chloride during pregnancy, we need to look for other sources of chloride.

I started looking into chloride because one blogger said that switching from her prescription prenatal to Vitafusion Prenatal Gummy Vitamins made her morning sickness nausea go away (although she still wishes for a way to cure her acid reflux, i.e., heartburn). If the prescription prenatal vitamin had iron in it, I can see how switching to a iron-free gummy vitamin instead would make her feel better. Discontinuing iron-containing prenatal vitamins has been shown to improve nausea and vomiting in pregnancy (https://www.ncbi.nlm.nih.gov/pubmed/19280488).

But maybe there is something else in the Vitafusion gummies that is actually helping her. The ingredient list for the Vitafusion gummy vitamins looks fairly standard for prenatal vitamins except for one ingredient: choline chloride, a compound of choline and chloride. Perhaps she already has hypochlorhydria at her present stage of pregnancy and so the low pH form of sulfite oxidase in her stomach is being blocked due to chloride depletion; if that is the case, then by taking a compound with supplemental chloride in it, she helped unblock the sulfite oxidase and thus facilitated the enzyme's carrying out its normal activity.

If chloride ingestion can lead to faster conversion of sulfite to sulfate, that could explain why salty foods and drinks--Saltines, potato chips, french fries, Gatorade, etc.--often help women with morning sickness feel better. Salt is a very good source of Cl-.

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