According to dr. Shattock, OP insecticides will inhibit any enzymes with an active serine site
In his article he mentioned four enzymes:
- tryptophan hydroxylase
- di-peptyl peptidase IV
I found the last enzyme very interesting because the Klimas article mentioned earlier by Hip, stated that di-peptyl peptidase IV (DPPIV) is low in CFS and is involved in the biologic effects of neuropeptide Y.
Recently, our group reported that soluble as well as cell surface associated dipeptidyl peptidase IV (DPPIV) is decreased in CFS cases relative to controls . NPYs biologic effects require interaction with its receptors. Native NPY 1-36 in the periphery is a major mediator of stress, responsible for prolonged vasoconstriction via Y1 receptors . By cleaving the N-terminal Tyr-Pro dipeptide from NPY, DPPIV generates the Y2/Y5 receptor agonist NPY 3-36, that loses its affinity for the Y1 receptor and is angiogenic and inhibitory of NE release [30,63]. The low DPPIV observed in CFS coupled with high NPY would favor the Y1 receptor agonist form of NPY
I'd like to comment on DPPIV, also known as CD26 in the immune system.
Lack of this enzyme has been found to be associated with food sensitivities to casein and gluten in autism patients. Some of the digestive enzyme products used in autism therefore include it.
As you may know, I believe that autism and ME/CFS are the same disorder from the biochemical perspective (symptoms and epidemiology differing only because of different ages at onset in relation to brain development and puberty). I think this is consistent with the fact that many PWCs are gluten and casein sensitive, and that Dr. Klimas's group has found low DPPIV in ME/CFS.
I have a hypothesis for the cause of the low DPPIV in autism and CFS. This hypothesis also applies to other secretory proteins that are found to be low in ME/CFS, including several of the peptide hormones (for examples, ACTH, antidiuretic hormone, and and growth hormone) as well as perforin. Here it is:
These proteins that show deficits all normally contain cysteine. When a protein is synthesized inside a cell, the amino acids are first joined together in an appropriate chain by the ribosomes within the cytosol. Then the chain is passed into the endoplasmic reticulum, where the tertiary structure of the protein is formed by linking cysteine residues together with their proper partners to form disulfide cystine bonds. If it is to be a secretory protein, it is then exported from the cell.
In order for this process to occur properly, the cysteine molecules must be maintained in their reduced state as cysteine, and not be allowed to bind together to form cystine until the appropriate stage of the process in the endoplasmic reticulum.
Here's where the problem arises in autism and CFS. Glutathione is depleted in the cytosol of cells. Without sufficient glutathione to control the redox potential in the cystosol, the cysteine molecules form disulfide bonds too early. This causes the quality control mechanism to send the malformed proteins to the proteasomes, which take them appart and recycle the amino acids. The result of this continuing recycling is that not enough of the proteins are formed.
The problem seems to be worst with proteins that contain a lot of cysteine residues. Perforin contains 20. DPPIV contains 12. It also seems to be worse for proteins that are made by cells that do not have a completely functioning transsulfuration pathway, and thus are not able to make cysteine from methionine, so that a scarcity of cysteine shows up first in them. Beside being an important constituent of these proteins, cysteine is also the rate-limiting amino acid for the synthesis of glutathione.
A counterexample is insulin. It is usually not low in ME/CFS, but does contain cysteine. I suggest that the reason it is O.K. is that it is made in the pancreas, and pancreatic cells do have a complete transsulfuration pathway.
DPPIV also has an important role (as CD26) on the lymphocytes. Lymphocytes do not have a complete transsulfuration pathway, as far as I know. So low CD26 in ME/CFS would again be consistent with this hypothesis.