Although essential to amino group transfer, decarboxylation, interconversion, and sundry manipulation of amino acids, the reactivity of this "friendly giant" must be held in abeyance until it is needed. It has been shown that while acetaldehyde has no effect on the synthesis of pyridoxal phosphate, it may accelerate its degradation by displacing this co-enzyme from binding proteins which protect it against hydrolysis [1].
Acetaldehyde has thus assumed another deleterious role by interfering with cellular reserves of a vital nutritional component. This can lead to deficiency symptoms which are indistinguishable from an actual paucity of dietary intake.
One of the cellular detoxification pathways for acetaldehyde is oxidation via the enzyme aldehyde dehydrogenase which emits acetic acid. Although normally considered to be a harmless molecular configuration relative to its parent aldehyde, accumulation of this weak acid, when acetaldehyde levels are high and chronic, can upset the pH balance of the cell [2]. Even the acetate itself may have a negative impact on PLP-based enzymes. Acetate has been shown to inhibit the recombination of PLP with glutamate apodecarboxylase [3].
When a cargo ship docks with the space station it must approach and latch with the hatch at just the right angle and alignment so that a good seal is obtained, its cargo can be transferred, and it can be dispatched for the return journey. Something similar happens within enzymes in the body where molecules temporarily attach themselves to latch points in the protein structure so that the desired chemical reaction may occur. If the substrates cannot position themselves properly within the enzyme, the chemical reaction that is essential just won't happen.
A common "latch" point in many of the diverse enzymes that utilize PLP as a cofactor is the amino group of an active site lysine amino acid. The aldehyde portion of PLP forms a Schiff base (carbon-nitrogen double bond) with the lysine residue:
In the cellular "inner space" small freely floating molecules of acetaldehyde have no problems drifting into reaction pockets of enzymes. For PLP reactive enzymes, they can form the Schiff base with the lysine residues, prevent PLP from assuming its requisite position in the enzymes and effectively render the enzymes useless [4]:
Structural ejection mechanisms that would normally recycle the enzyme for another reaction may not be able to remove the tiny acetaldehyde molecules which remain there as permanent inhibitors of the enzymatic pathways. In the space station analogy, think of a small piece of space junk getting stuck in the cargo bay seals preventing a uniform docking maneuver.
The aldehyde commonality between acetaldehyde and PLP means that not only can acetaldehyde create a deficiency state of PLP even in the presence of adequate dietary intake, it can shut down enzymatic PLP-dependent pathways even when PLP is sufficiently available as a co-factor. Deficiency symptoms can then be expected to manifest that may respond to higher than normal intake of B6, something that attempts to compensate for this disruption. However, even the conditions that appear to be associated with a B6 deficiency may not be completely resolved by B6 supplementation alone. This confusion arises since the disruptive influence of acetaldehyde includes but is not limited to PLP.
Acetaldehyde is interfering with other essential biochemical functions as well. This is why scavengers (such as Wondro) that intercept the acetaldehyde before it has had a chance to attack vulnerable pathways or antifungals (such as garlic) that reduce the production of acetaldehyde or energetic signals (such as homeopathic sulfur) that shift yeast from its budding fermentative state appear to achieve superior results in a wide variety of conditions. They are working at the upstream source of the difficulty, rather than downstream at the level of the deficiency symptoms. Chasing the symptoms using drugs or nutritional supplements only provides temporary relief since the sporadic low-dosage acetaldehyde exposure continues uninterrupted.
The Enzyme Commission [5] list of PLP-dependent activities [6] is hundreds of entries in length. Of these pathways each and every one that is present in the body is a potential candidate for acetaldehyde-mediated PLP interference. As well, since many PLP-dependent enzymes are working at the level of amino (fundamental building blocks of proteins) group transfer and conversion, a critical precursor step in a multi-step pathway may be impaired. This means that the subsequent enzymatic processes may also be affected even though they are not specifically dependent upon PLP themselves.
PLP deficiency has been causally implicated in several clinical disorders in the alcoholic patient, including peripheral neuropathy [7], convulsions [8], sideroblastic anemia [9], and liver disease [10]. Acetaldehyde is an intermediate in the hepatic enzymatic breakdown of ingested alcohol but even low levels of yeast-released acetaldehyde may be just as, or even more, damaging because of the locales where it is released by colonizing yeast cells.
[1] Lumeng L, "The Role of Acetaldehyde in Mediating the Deleterious Effect of Ethanol on Pyridoxal 5′-Phosphate Metabolism", J Clin Invest. 1978 August; 62(2): 286–293.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC371765
[2] Roe et al., "Perturbation of Anion Balance during Inhibition of Growth of Escherichia coli by Weak Acids", J Bacteriol. 1998 February; 180(4): 767–772.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC106953
[3] Fonda ML, "The effect of anions on the interaction of pyridoxal phosphate with glutamate apodecarboxylase.", Archi Biochem Biophys. 1975 Oct;170(2):690-7.
http://www.ncbi.nlm.nih.gov/pubmed/242264
[4] Mauch TJ et al., "Covalent binding of acetaldehyde selectively inhibits the catalytic activity of lysine-dependent enzymes.", Hepatology. 1986 Mar-Apr;6(2):263-9.
http://www.ncbi.nlm.nih.gov/pubmed/2937708
[5] Moss GP, "Enzyme Nomenclature", School of Biological and Chemical Sciences, Queen Mary University of London.
http://www.chem.qmul.ac.uk/iubmb/enzyme/
[6] Ibid., "pyridoxal"
http://www.googlesyndicatedsearch.com/u/queenmary?q=pyridoxal&hl=en&hq=inurl:...
[7] Dellon AL et al., "Experimental model of pyridoxine (B6) deficiency-induced neuropathy.", Ann Plast Surg. 2001 Aug;47(2):153-60.
http://www.ncbi.nlm.nih.gov/pubmed/11506323
[8] Lerner AM et al., "Association of pyridoxine deficiency and convulsions in alcoholics.", Proc Soc Exp Biol Med. 1958 Aug-Sep;98(4):841-3.
http://www.ncbi.nlm.nih.gov/pubmed/13591361
[9] Hines JD et al., "Studies on the pathogenesis of alcohol-induced sideroblastic bone-marrow abnormalities.", N Engl J Med. 1970 Aug 27;283(9):441-6.
http://www.ncbi.nlm.nih.gov/pubmed/5434110
[10] Labadarios et al., "Vitamin B6 deficiency in chronic liver disease--evidence for increased degradation of pyridoxal-5'-phosphate.", Gut. 1977 January; 18(1): 23–27.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1411256