Re: Detoxifying acetaldahyde

Industrial waste-water methylmercury was eventually identified as the the cause of the devastating neurological symptoms in Minamata, Japan that appeared starting in 1956. Afflicted individuals had mercury levels in hair samples that were hundreds of times greater than for the average of those living outside of the affected region. The ultimate toxicity of this organic heavy metal compound is not disputed as other incidents around the world (Niigata, Japan 1965; Basra, Iraq 1971) involving methylmercury exposure have resulted in similar mass poisonings with a high fatality rate.

Methylmercury has a chemical formula of CH3Hg+. Since it is a positively charged cation, it will combine with anions such as chloride, hydroxide and nitrate. Ingested methylmercury also has a high affinity for sulfur-containing compounds such as the amino acid cysteine [1] and proteins/peptides displaying cysteine residues where it forms a covalent bond with the sulfhydryl group. Acetaldehyde (CH3CHO) also finds cysteine and associated sulfhydryls irresistible [2].

The structures of these two substances side by side highlight their size and shape similarities:



Acetaldehyde is not a cation like methylmercury. However, as a result of the higher electronegativity of oxygen than carbon in the acetaldehyde molecule, the carbonyl group is polarized. The carbon atom has a partial positive charge, and the oxygen atom has a partial negative charge:



This renders acetaldehyde highly reactive towards a wide variety of attractive groups in a fashion that might mimic the heavy metal cations. The relatively small hydrogen atom connected to the carbonyl carbon presents little steric hindrance to the formation of complexes at this carbon site.

This prolific bonding ability is emphasized by the many classes of reactions that occur involving acetaldehyde [3]:

• 1,2-additions with nucleophilic reagents yielding two-carbon extended secondary alcohols

• aldol condensation with wide variety of enolates

• Mannich reactions for Schiff base formation

• Pictet-Spengler ring-forming reactions

• Lindgren (Pinnick) oxidation to carboxylic acid

• mixed Tishchenko dismutation reactions

• with itself to form paraldehyde (a trimer) and metaldehyde (a tetramer)

• even with water to form a hydrate



[The hydration of acetaldehyde is interesting in that it may provide an explanation for why water helps in some cases of acid reflux. If the acid reflux is triggered by yeast-released acetaldehyde irritation of esophageal mucous membranes, then water may alleviate this by changing it into a less reactive form. However, the reaction is rapidly reversible allowing acetaldehyde to return for subsequent damage after only transient water scavenging. Also, water alone does not prevent the yeast source of the acetaldehyde from continuing to produce it.]

Not all of these reactions occur within the body but even a subset of the list above is enough to provide unrestrained acetaldehyde with more than ample opportunities for disruption of whatever aspects of the body's biochemistry that it happens to come into contact with.

Both acetaldehyde and methylmercury can be scavenged by the body's innate chelating cysteine-rich metallothioneins [4,5]. Note the abundance of (yellow) sulfur atoms in the structure:



However, the competence of this system may become overloaded when toxic exposure is chronic or high and is dependent upon dietary intake and absorption of sulfur-bearing amino acids, something that can be disrupted by either acetaldehyde or methylmercury:

See "Cysteine + Acetaldehyde" //www.curezone.org/forums/fm.asp?i=1973900

See "Methionine + Acetaldehyde" //www.curezone.org/forums/fm.asp?i=1977201

Methylmercury has a high affinity for the selenohydryl group and selenide [6]. This can create an intracellular selenium deficiency for selenoenzymes where selenium appears in a cysteine residue instead of sulfur (as part of the 21st proteinogenic amino acid selenocysteine).

Even normal functioning of mitochondrial cellular energy processes can result in the appearance of reactive oxygen species:

See "Hydrogen Peroxide/Lipid Hydroperoxide" //www.curezone.org/forums/fm.asp?i=1976523

One of the major responsibilities of the cellular glutathione redox pool (GSH/GSSG) is ensuring that these damaging species do not accumulate. The main reaction catalyzed by glutathione peroxidase is:

2 GSH + H2O2 (Hydrogen-Peroxid) ---> GS-SG + 2 H2O

which neutralizes hydrogen peroxide back to water, and a related pathway catalyzed by phospholipid-hydroperoxide glutathione peroxidase:

2 GSH + Lipid Hydroperoxide ---> GS-SG + Lipid + 2 H20

returning the dangerous lipid hydroperoxide to its lipid state before it can split into another free radical and malondialdehyde.

Even when glutathione is amply available in its reduced form (GSH), methylmercury can prevent these reactions by rendering glutathione peroxidase [7] (and other seleno-enzymes) non-functional via a post-transcriptional defect for selenocysteine [8]. This leads to intolerable levels of oxidative stress within the contaminated cells and cellular dissociation (apoptosis) with potentially fatal outcomes.

Fortunately, acetaldehyde exposure does not lead to this rapid type of collapse of the glutathione redox sufficiency [9]. However, the similarities between symptomology in candidiasis syndrome, acetaldehyde poisoning, and heavy metal toxicity:

See "Daily Toxic Spill" //www.curezone.org/forums/fm.asp?i=1963617

and the size, shape and polar nature commonalities of acetaldehyde in relation to methylmercury suggest that there are some common pathways under duress in each of these conditions.

The ability of yeast-released acetaldehyde to disrupt sulfur-based metabolism and erode both the Cys/CySS and GSH/GSSG redox pools leading to increasing levels of oxidative stress has already been explored:

See "Cys/CySS Redox Pool" //www.curezone.org/forums/fm.asp?i=1975696

See "GSH/GSSG" //www.curezone.org/forums/fm.asp?i=1977665

Since the seleno-enzyme glutathione peroxidase is the major toxicity attack point for methylmercury, perhaps both acetaldehyde and methylmercury contribute to the downward spiral of an organism into disease mediated by increased oxidative stress but on different time scales (years in the case of low-dose yeast-released acetaldehyde and weeks/months in the case of acute methylmercury exposure). Another difference to factor into this model is that there are other scavenging mechanisms for aldehydes (e.g. aldehyde dehydrogenase, carnosine) that can reduce the impact of acetaldehyde. Even in the case of methylmercury poisoning there is a silent latency symptom-free period between the time of first exposure and the manifestation of identifiable neurological symptoms [10].

In situations where there is combined exposure to both methylmercury (even in trace amounts) and yeast-released acetaldehyde, there may be a synergistic deleterious effect via competition for the resources in the body designed to deal with this type of toxicity:

See "Autism" //www.curezone.org/forums/fm.asp?i=1978485


[1] Roos DH et al., "Complex methylmercury-cysteine alters mercury accumulation in different tissues of mice.", Bas Clin Pharmacol Toxicol. 2010 Oct;107(4):789-92. http://www.ncbi.nlm.nih.gov/pubmed/20486922

[2] Medina VA et al., "Covalent binding of acetaldehyde to hepatic proteins during ethanol oxidation.", J Lab Clin Med. 1985 Jan;105(1):5-10.
http://www.ncbi.nlm.nih.gov/pubmed/3968465

[3] Encyclopedia of Reagents for Organic Synthesis, "Acetaldehyde"
http://www.wiley.com/legacy/wileychi/eros/acetaldehyde.html

[4] Hao Q et al., "Aldehydes release zinc from proteins. A pathway from oxidative stress/lipid peroxidation to cellular functions of zinc.", FEBS J. 2006 Sep;273(18):4300-10. Epub 2006 Aug 23.
http://www.ncbi.nlm.nih.gov/pubmed/16930132

[5] Yao CP et al., "Metallothioneins attenuate methylmercury-induced neurotoxicity in cultured astrocytes and astrocytoma cells.", Ann N Y Acad Sci. 1999;890:223-6.
http://www.ncbi.nlm.nih.gov/pubmed/10668428

[6] Sugiura Y et al., "Selenium protection against mercury toxicity: high binding affinity of methylmercury by selenium-containing ligands in comparison with sulfur-containing ligands.", Bioinorg Chem. 1978 Aug;9(2):167-80.
http://www.ncbi.nlm.nih.gov/pubmed/698281

[7] Franco JL et al., "Methylmercury neurotoxicity is associated with inhibition of the antioxidant enzyme glutathione peroxidase.", Free Radic Biol Med. 2009 Aug 15;47(4):449-57. Epub 2009 May 18.
http://www.ncbi.nlm.nih.gov/pubmed/19450679

[8] Usuki F et al., "Post-transcriptional defects of antioxidant selenoenzymes cause oxidative stress under methylmercury exposure.", J Biol Chem. 2011 Feb 25;286(8):6641-9. Epub 2010 Nov 24.
http://www.ncbi.nlm.nih.gov/pubmed/21106535

[9] Pivetta LA et al., "Acetaldehyde does not inhibit glutathione peroxidase and glutathione reductase from mouse liver in vitro.", Chem Biol Interact. 2006 Feb 25;159(3):196-204. Epub 2006 Jan 4.
http://www.ncbi.nlm.nih.gov/pubmed/16387289

[10] Weiss B et al., "Silent latency periods in methylmercury poisoning and in neurodegenerative disease.", Environ Health Perspect. 2002 Oct;110 Suppl 5:851-4.
http://www.ncbi.nlm.nih.gov/pubmed/12426145