Re: Detoxifying acetaldahyde

Sulfur is a very versatile atom. Its electron cloud, capable of forming covalent bonds, can be excited so that it can assume valences of both 4 and 6 as well as its usual valence of 2. This flexibility shows up in the body in regions that depend upon elasticity, motion, and stickiness. More often than not it is also found in a cysteine residue in an enzymatic reaction pocket designed to hold a substrate just long enough for the atomic reconfiguration specific to the enzyme to be carried out and the enzyme product ejected -- transient metabolite binding.

There are only two amino acids that contain sulfur: cysteine and methionine. Dietary cysteine is a potential target for direct acetaldehyde attack:

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

The position of the sulfur atom in methionine:



does not appear to be as attractive a target for acetaldehyde binding as it is for cysteine [1].

This implies that dietary methionine could take up some slack in relation to acetaldehyde-mediated cysteine disruption. Cysteine is classed as a semi-essential amino acid for this very reason, that it can usually be synthesized by the human body from methionine. However, this pathway is not fully developed in children [2] making them more vulnerable to aberrations in cysteine metabolism [3,4]. The functional pathway from methionine to cysteine involves conversion of the intermediate homocysteine:



into cystathionine using the enzyme cystathionine-beta-synthase with pyridoxal-phosphate as a cofactor. However, pyridoxal-phosphate is an aldehyde and the carbonyl group similarity in acetaldehyde may interfere with this step in the pathway from methionine to cysteine [5]. Excess homocysteine that can't make the transition to cysteine should be recycled back to methionine via the enzyme methionine synthase with vitamin B12 as a cofactor, but acetaldehyde inhibits this transition as well by forming an inhibiting covalent adduct with the enzyme [6].

With cysteine essentially functioning as an acetaldehyde scavenger, the methionine that the body is using to try and rebuild dwindling cysteine reserves gets stuck as homocysteine and can't go forward or back. This is supported by the association of hyperhomocysteinemia with alcoholism [7] where acetaldehyde is a known by-product of alcohol metabolism in the liver.

Although homocysteine is not an amino acid, it looks like one. The structural similarities between the intermediate homocysteine and methionine can create problems for protein synthesis with the result that excess levels of homocysteine are cytotoxic [8].

In this model, not only does yeast-released acetaldehyde interfere directly with cysteine, it also blocks the secondary pathways from methionine to cysteine and from homocysteine back to methionine producing an accumulation of a toxic substance in the process. The body's sulfur-based metabolism is now officially in big trouble!

[1] Yamashita K et al., "Acetaldehyde Removal from Indoor Air through Chemical Absorption Using L-Cysteine.", Int J Environ Res Public Health. 2010 September; 7(9): 3489–3498.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2954559

[2] Imura K et al., "Amino acid metabolism in pediatric patients.", Nutrition. 1998 Jan;14(1):143-8.
http://www.ncbi.nlm.nih.gov/pubmed/9437700

[3] James SJ et al., "Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism.", Am J Clin Nutr. 2004 Dec;80(6):1611-7.
http://www.ncbi.nlm.nih.gov/pubmed/15585776

[4] Bradstreet JJ et al., "Biomarker-guided interventions of clinically relevant conditions associated with autism spectrum disorders and attention deficit hyperactivity disorder.", Altern Med Rev. 2010 Apr;15(1):15-32.
http://www.ncbi.nlm.nih.gov/pubmed/20359266

[5] Lumeng L, "The role of acetaldehyde in mediating the deleterious effect of ethanol on pyridoxal 5'-phosphate metabolism.", J Clin Invest. 1978 Aug;62(2):286-93.
http://www.ncbi.nlm.nih.gov/pubmed/27531

[6] Barak AJ et al., "Methionine synthase. a possible prime site of the ethanolic lesion in liver.", Alcohol. 2002 Feb;26(2):65-7.
http://www.ncbi.nlm.nih.gov/pubmed/12007580

[7] Carvo ML et al., "Hyperhomocysteinemia in chronic alcoholism: relations to folic acid and vitamins B(6) and B(12) status.", Nutrition. 2000 Apr;16(4):296-302.
http://www.ncbi.nlm.nih.gov/pubmed/10758367

[8] Jakubowski H, "Molecular basis of homocysteine toxicity in humans.", Cell Mol Life Sci. 2004 Feb;61(4):470-87.
http://www.ncbi.nlm.nih.gov/pubmed/14999406 Tweet