I am honing in on the cause of my disorder, I think. I am betting it is either a defect in PEMT or a defect in agmatine transport or closely related to these.
Previously I posted that I thought a defect in or related to agmatine transport may be the cause of my disorder and that I thought malfunctioning pathways were probably present in my disorder.
These malfunctioning pathways included presumed over-expression of pathways from:
1. Proline to ornithine decarboxylase to polyamines; and
2. Arginine to NOS to NO to cGMP to cGMP dependent protein kinase.
Agmatine regulates these pathways in the right way. Agmatine is transported by hMATE1 which is a deletion in Smith Magenis syndrome at 17p11.2. I then found there is a pattern of Smith Magenis symptoms and conditions in me and my family on my father's side. Also, I now know a defect in hMATE1 would directly explain my high urinary creatinine and high urinary B3 metabolite and after taking agmatine supplements I suffered severe watery diarrhoea and other side effects.
However, PEMT is also a deletion in Smith Magenis Syndrome at 17p11.2 and also regulates ornithine decarboxylase activity. PEMT produces phosphatidyl choline, DHA, glucose and adenosylhomocysteine which produces homocysteine.
I have been investigating why B-group supplements I took along with fish oil were so effective in effectively curing my psychosis. I took each supplement individually and the ones that were most effective on their own (though not as good as the B-group) were lecithin, avena sative and folic acid. Lecithin contains phosphatidyl choline, avena sativa up-regulates ceramides which inhibit the enzyme that PEMT acts on to produce phosphatidyl choline. DHA is in fish oil. Folic acid up-regulates phosphatidyl choline. I have also long thought that glucose may be counter-intuitively neuroprotective in my family. That is all anecdotal, but is obviously persuasive to me.
However, I now find that an alternative route to homocysteine is via cystathionine. For some time I have wondered if my abnormal serine (low on the B-group supplements) was connected to cystathionine because a paper reports some B-vitamins result in lowered serine in some patients with kidney problems and the writers suggested this was directly connected to cystathionine. I also have high B6 and abnormal is usually associated with abnormalities in homocystein. This gives me some objective evidence that I could be right about PEMT. The next step is to trial ceramides, pshosphatidyl choline, DHA, serine and the B vitamins linked to lowering serine and to try to get these metabolites tested.
I am not a believer in coincidences. If I am right, I think there must be a direct connection between agmatine and the activity of PEMT. There are some suggestions this may be the case, but no direct research on this that I can find, as yet.
The sad thing is that I think that many psychiatric and neurodegenerative disorders have multiple different metabolic/enzymatic/protein causes, but there are few experts out there looking for the individual causes of these disorders based on what an individual's abnormal results tell them is going wrong in their metabolism.
All of the above is from memory and I am no doctor, so do not rely on it without first properly verifying the information. Obviously I think B-supplements can be an effective treatment in some cases, but these cases are rare. Only investigate your disorder and trial supplements under the supervision of your doctor. Supplements may interact with medications and usually have side effects.