Wednesday, May 30, 2012

Biological effects of silicofluorides: effects of Cholinesterase Inhibition

Effects of Cholinesterase Inhibition: 
Professor Roger D. Masters 

The implications for human health of this SiF-induced bio-mechanism are numerous and in some instances can be extremely serious.  One of the most important of these effects concerns the interference with cholinesterases.   While acetylcholinesterase (AChE) is known due to its regulatory role for acetylcholine (a neurotransmitter with multiple functions including activating motor behavior), even today the role of butyryl-cholinesterase (BChE) and its relationship to AChE is not entirely understood:

       “Human tissues have two distinct cholinesterase activities: acetylcholinesterase and
         butyrylcholinesterase. Acetylcholinesterase functions in the transmission of nerve 
         impulses, whereas the physiological function of butyrylcholinesterase remains

At least one function believed to be served by BChE is to protect AChE by scavenging toxins.

        “Butyrylcholinesterase must be differentiated from acetylcholinesterase, which
          cannot hydrolyse succinylcholine. The physiological action of butyryl-
          cholinesterase remains unknown, although it can hydrolyse many drugs.”[ii]

It is not inconceivable that the role of BChE as a protector of AChE goes beyond the capacity to hydrolyze drugs to a sacrificial role in absorbing heavy metals. In any case, powerful inhibition of BChE by SiF would indirectly modify an indirect impact on the proper function of AChE. Moreover, their interaction has been associated with brain dysfunction:

       “Evidence about nonclassic functions of acetyl- (AChE) and butyryl-cholinesterase
         (BChE) during embryonic development of vertebrate brains is compared with
         evidence of their expression in Alzheimer disease (AD). Before axons extend
         in the early neural tube, BChE expression shortly precedes the expression of
         AChE. BChE is associated with neuronal and glial cell proliferation, and it may
         also regulate AChE. AChE is suggested to guide and stabilize growing axons.
         Pathologically, cholinesterase expression in AD shows some resemblance to
         that in the embryo.”[iii]

Regarding AChE inhibition, Westendorf found that fluoride released by NaF acted only in the competitive mode, but SiF had a much more powerful effect and acted in two modes. The first mode was competitive, as expected, due to the 67 % of the SiF fluoride released as free fluoride. In addition, however, the non-dissociated fluoride-bearing SiF residue enhanced net inhibition significantly in the non-competitive mode. Westendorf suggested that the species [SiF2(OH)42- mentioned above somehow distorted the morphology of the AChE molecule but he did not offer an explanation for how that occurred. Without referring to Westendorf’s work at all, a hint of an explanation for this effect appeared in the English language literature a few years later.[iv]

The “Margolis mechanism” discussed by Iler [v] suggests how low molecular weight poly-silicic acid oligomers formed in the blood-stream could disrupt polypeptide chain morphology:

        “The effect of silica was described by Margolis as due to the adsorption and
         denaturation of a globular protein, the Hageman factor. The proposed mechanism
         was that on sufficiently large particles or on flat  surfaces of silica, the protein
         molecule was stretched out of shape by adsorption forces as it formed a
         monolayer on the surface. When the silica particles were very small, the molecular
         segments of the protein could become attached to different particles without
         segment stretching…When protein is adsorbed on a larger silica particle or a
         coherent aggregate of smaller particles, the chain  stretched and certain internal
         hydrogen bonds which hold the protein molecule in a specific configuration
         are broken. On small single particles no such stretching occurs.”
Any of the partially dissociated SiF species just described -- e.g., [SiF2(OH)4]2-, SiF4, or SiF2(OH)2 derived from SiF4 -- would be candidates for producing low molecular weight polysilicic acid oligomers in the blood stream, after crossing over from the stomach at pH around 2. Most enzymes are globular proteins, so many enzymes besides AChE would be likely to experience at least noncompetitive inhibition by the “Margolis mechanism.”

[i] Allderdice PW et al; “The cloned butyrylcholinesterase (BCHE) gene maps to a single chromosome site, 3q26”; Genomics 1991 Oct;11(2):452-4.

[ii] C. Lejus, et al; “Cholinesterases”; Ann Fr Anesth Reanim 1998;17(9):1122-35.

[iii] P. G. Layer,  “Nonclassical roles of cholinesterases in the embryonic brain and possible links to Alzheimer disease”; Alzheimer Dis Assoc Disord 1995;9 Suppl 2:29-36).

[iv] L. Margolis L; Nature 264, 620, 1976, cited in Iler Ralph K.; “The Chemistry of Silica; Solubility, Polymerization, Colloid and Surface Properties, and Biochemistry”; John Wiley & Sons; New York, 1979.

[v] Ibid., p. 764.

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