Post by nyxie63 on Sept 6, 2008 3:16:24 GMT -8
LE, if this is in the wrong place, feel free to move it.
Putting this here so I don't forget what I was thinking. Would appreciate your thoughts on it as well.
Minor lightbulb moment? We'll see. Need to get this all down somewhere so I can look at it when my mind doesn't resemble a dustbunny convention.
Excerpt from www.townsendletter.com/FebMar2006/lyme0206.htm (emphasis mine)
Because many of the symptoms of Lyme disease involve the nervous system, it was speculated that the spirochete produced a toxin that disrupted normal nerve function. Through the use of DNA manipulations and a database of known protein toxin DNA sequences, a match was made with a selected Borrelia burgdorferi (Bb) gene and a specific toxin in the database. Protein generated from this cloned Bb gene was examined biochemically and found to have characteristics similar to that of botulinum, the toxin of Clostridium botulinum, a zinc endoproteinase.
The toxin from Bb belongs to a family of toxic proteins known as "zinc endoproteinases" or metalloproteases, and includes the toxin from the organism causing tetanus as well as those from many other well-known infectious diseases. The structures of this family of toxins are all very similar, as determined by x-ray crystal analysis. They all contain zinc and perform the same proteolytic function, namely, cleaving the chemical (covalent) bond between two specific amino acids in a particular protein found in nerve cells. The substrate for this enzyme is very large, implying that any inhibitor of enzyme activity blocking the entry of the substrate into the active site must also be very large.
Excerpt from www.immunedisease.com/US/patients/IDF/igg_subclass.html:
While all the IgG subclasses contain antibodies, each subclass serves somewhat different functions in protecting the body against infection. For example, the IgG1 and IgG3 subclasses are rich in antibodies against proteins such as the toxins produced by the diphtheria and tetanus bacteria, as well as antibodies against viral proteins. In contrast, antibodies against the polysaccharide (complex sugar) coating (capsule) of certain disease-producing bacteria (e.g. the pneumococcus and Haemophilus influenzae) are predominantly of the IgG2 type. Some of the IgG subclasses can easily cross the placenta and enter the unborn infant's bloodstream, while others do not. Antibodies of certain IgG subclasses interact readily with the complement system, while others interact poorly, if at all, with the complement proteins. Thus, an inability to produce antibodies of a specific subclass may render the individual susceptible to certain kinds of infections but not others.
Now here's where it's starting to click. Don't know if it means anything, but the similarities of the Bb toxins to tetanus, plus the inability of those with IgG1 and/or IgG3 subclass deficiencies to create antibodies to tetanus, makes me wonder if that's why some don't create certain antibodies and perhaps why some lyme IgMs don't convert to IgG in spite of having had lyme for long periods.
The link between similarities in basic toxin structure plus a selective IgG subclass deficiency may be a breadcrumb trail worth following.
Also wondering if/how intracellular zinc levels and zinc consumption play into this. Do the bacteria draw zinc from their hosts in the creation of the toxins, rather like the bacteria uses magnesium? Would altering the amount of consumption of zinc and/or copper change anything, since these two minerals form a balancing act in the body?
Hmmmmm..........
edited to fix formatting
Putting this here so I don't forget what I was thinking. Would appreciate your thoughts on it as well.
Minor lightbulb moment? We'll see. Need to get this all down somewhere so I can look at it when my mind doesn't resemble a dustbunny convention.
Excerpt from www.townsendletter.com/FebMar2006/lyme0206.htm (emphasis mine)
Because many of the symptoms of Lyme disease involve the nervous system, it was speculated that the spirochete produced a toxin that disrupted normal nerve function. Through the use of DNA manipulations and a database of known protein toxin DNA sequences, a match was made with a selected Borrelia burgdorferi (Bb) gene and a specific toxin in the database. Protein generated from this cloned Bb gene was examined biochemically and found to have characteristics similar to that of botulinum, the toxin of Clostridium botulinum, a zinc endoproteinase.
The toxin from Bb belongs to a family of toxic proteins known as "zinc endoproteinases" or metalloproteases, and includes the toxin from the organism causing tetanus as well as those from many other well-known infectious diseases. The structures of this family of toxins are all very similar, as determined by x-ray crystal analysis. They all contain zinc and perform the same proteolytic function, namely, cleaving the chemical (covalent) bond between two specific amino acids in a particular protein found in nerve cells. The substrate for this enzyme is very large, implying that any inhibitor of enzyme activity blocking the entry of the substrate into the active site must also be very large.
Excerpt from www.immunedisease.com/US/patients/IDF/igg_subclass.html:
While all the IgG subclasses contain antibodies, each subclass serves somewhat different functions in protecting the body against infection. For example, the IgG1 and IgG3 subclasses are rich in antibodies against proteins such as the toxins produced by the diphtheria and tetanus bacteria, as well as antibodies against viral proteins. In contrast, antibodies against the polysaccharide (complex sugar) coating (capsule) of certain disease-producing bacteria (e.g. the pneumococcus and Haemophilus influenzae) are predominantly of the IgG2 type. Some of the IgG subclasses can easily cross the placenta and enter the unborn infant's bloodstream, while others do not. Antibodies of certain IgG subclasses interact readily with the complement system, while others interact poorly, if at all, with the complement proteins. Thus, an inability to produce antibodies of a specific subclass may render the individual susceptible to certain kinds of infections but not others.
Now here's where it's starting to click. Don't know if it means anything, but the similarities of the Bb toxins to tetanus, plus the inability of those with IgG1 and/or IgG3 subclass deficiencies to create antibodies to tetanus, makes me wonder if that's why some don't create certain antibodies and perhaps why some lyme IgMs don't convert to IgG in spite of having had lyme for long periods.
The link between similarities in basic toxin structure plus a selective IgG subclass deficiency may be a breadcrumb trail worth following.
Also wondering if/how intracellular zinc levels and zinc consumption play into this. Do the bacteria draw zinc from their hosts in the creation of the toxins, rather like the bacteria uses magnesium? Would altering the amount of consumption of zinc and/or copper change anything, since these two minerals form a balancing act in the body?
Hmmmmm..........
edited to fix formatting
