Re: Detoxifying acetaldahyde

Selenocysteine is known as the twenty-first proteinogenic amino acid. Its structure is identical to cysteine except that it has the element selenium where sulfur would normally reside [1]. The high reactivity of selenium makes it suitable for rapid turnover enzymes such as glutathione peroxidase that clear cells of reactive oxygen species before they pollute the cellular environment. However, this reactivity also means that no free pool of selenocysteine exists in a cell -- it would be too damaging to the cell. This on-demand synthesis makes this amino acid vulnerable not only to (rare) dietary selenium deficiencies but also to disruptions in the pathway that creates it.

Selenocysteine synthesis occurs on a specialized transfer RNA adaptor molecule that incorporates selenium into a serine residue via the pyridoxal-5'-phosphate (PLP)-dependent enzyme selenocysteine synthase prior to the inclusion of this modified amino acid into the target protein.



Since this unusual amino acid has no corresponding direct DNA code, it is selected by the UGA (stop) codon during a special translational sequence. When selenocysteine isn't available, either because of a selenium deficiency or because of selenocysteine synthase failure, translation of a selenoprotein terminates at the UGA codon instead of incorporating the modified amino acid. This results in a truncated, dysfunctional selenoenzyme.

Methylmercury can rapidly degrade this pathway by creating an intracellular selenium deficiency:

See "Methylmercury" //www.curezone.org/forums/fm.asp?i=1979925

Pulsed low-dosage exposure to yeast-released acetaldehyde may influence this same pathway incrementally over a longer period but can attack from multiple directions. The potential for acetaldehyde interference involves not only diminishing the amount cysteine available for the synthesis of glutathione itself:

See "Acetaldehyde + Glutathione" //www.curezone.org/forums/fm.asp?i=1977665

but also inducing a pyridoxal deficiency as well as possibly interfering with the PLP-dependent enzyme that produces selenocysteine, something essential for the selenoenzyme glutathione peroxidase:

See "Acetaldehyde + PLP" //www.curezone.org/forums/fm.asp?i=1982110

Since glutathione peroxidase is the major waste removal system for reactive oxygen species of a cell:

See "Glutathione Peroxidase" //www.curezone.org/forums/fm.asp?i=1979925

without a functional glutathione peroxidase pathway, a cell is susceptible to accumulation of this kind of nasty garbage culminating in cellular death (apoptosis). Although it might seem that supplementation with glutathione would help in this regard, oral absorption is minimal [2] and even when glutathione itself is available, the pathway won't work if the selenoenzyme that uses it is damaged.

The entire subclass of selenoenzymes, even those that do not directly utilize PLP as a cofactor themselves, are still dependent upon PLP because of their requirement for the quirky amino acid selenocysteine, synthesized by the PLP-dependent enzyme selenocysteine synthase. This means that acetaldehyde through PLP disruption can indirectly have a negative impact on ALL of the body's selenium metabolism [3].

The iodothyronine deiodinases that activate and deactivate thyroid hormones belong to this class of selenoenzymes. If the T4 and T3 hormones manipulated by these deiodinases are not being regulated properly, hypothyroidism can disrupt gene expression in practically every cell in the body [4].

The mammalian thioredoxin reductases [5] are a family of selenium-containing enzymes involved in the regulation of cellular redox protein thioredoxin and hence are involved in protection against oxidant injury, cell growth and transformation, and the recycling of ascorbate from its oxidized form. Whereas proteins in the extracellular environment or on the cell surface are rich in stabilizing disulfides (the oxidized state):

See "Disulfide Bonds" //www.curezone.org/forums/fm.asp?i=1958887

the inside of the cell abounds with proteins that contain many free sulfhydryl groups (the reduced state). Thioredoxin reductase is responsible for rectifying the cross-linking oxidation of sulfur-bearing proteins inside the cell. Not only does acetaldehyde find free sulfhydryl groups attractive targets for damage, it may interfere with the selenium-based management system that attempts to regulate them [6].

If an OPK (Orthomolecular Psychokinesiology) test [7] indicates that you are deficient in selenium, then Brazil nuts are a particularly good dietary source [8]. Intake should be judiciously monitored (too much is as bad as too little) and reduced when OPK biofeedback indicates that levels have stabilized.

There is so much interdependence amongst biochemical systems in the body, that impairment in any one of them can have consequences in a myriad of other pathways. With its ability to disrupt sulfur metabolism and pyridoxal metabolism, acetaldehyde can impact selenium metabolism as well. Regardless of the starting point you choose when you follow unscavenged acetaldehyde throughout the body's intricate biochemical network, just like "sugar in the gas tank", you end up with dysfunction leading to disease.

[1] Nauser T et al., "Why do proteins use selenocysteine instead of cysteine?", Amino Acids. 2012 Jan;42(1):39-44. Epub 2010 May 13.
http://www.ncbi.nlm.nih.gov/pubmed/20461421

[2] Witschi A et al., "The systemic availability of oral glutathione.", Eur J Clin Pharmacol. 1992;43(6):667-9.
http://www.ncbi.nlm.nih.gov/pubmed/1362956

[3] Kryukov GV et al., "Characterization of mammalian selenoproteomes.", Science. 2003 May 30;300(5624):1439-43.
http://www.ncbi.nlm.nih.gov/pubmed/12775843

[4] Wu Y et al., "Gene regulation by thyroid hormone.", Trends Endocrinol Metab. 2000 Aug;11(6):207-11.
http://www.ncbi.nlm.nih.gov/pubmed/10878749

[5] Arner ES et al., "Physiological functions of thioredoxin and thioredoxin reductase.", Eur J Biochem. 2000 Oct;267(20):6102-9.
http://www.ncbi.nlm.nih.gov/pubmed/11012661

[6] Moos PJ et al., "Electrophilic prostaglandins and lipid aldehydes repress redox-sensitive transcription factors p53 and hypoxia-inducible factor by impairing the selenoprotein thioredoxin reductase.", J Biol Chem. 2003 Jan 10;278(2):745-50. Epub 2002 Nov 6.
http://www.ncbi.nlm.nih.gov/pubmed/12424231

[7] "Deficient or What?", In Astrophysiology...and Yeast, 2011.
http://www.scribd.com/doc/74090699
http://www.epubbud.com/book.php?g=7JQU45V8

[8] Ip C et al., "Bioactivity of selenium from Brazil nut for cancer prevention and selenoenzyme maintenance.", Nutr Cancer 1994;21(3):203-12.
http://www.ncbi.nlm.nih.gov/pubmed/8072875


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