Phosphoinositides and ME

Germain et al:

"Another hypothesis that could be drawn from the pathway analysis concerns the glycerophospholipid metabolism, as we observed five altered metabolites involved in biological membrane composition. Phosphoinositides are phospholipids that play critical roles in the brain and the spinal cord and peripheral nerves, by being involved in cell regulation and membrane dynamics."

I believe this hypothesis is true and very important.

Phosphoinositides (PIs) are generated in the PI-cycle. The first step in the PI-cycle is the conversion of diacylglycerol (DAG) to phosphatidic acid (PA) via the enzyme diacylglycerol kinase (DGK).

The last step is genration of PIP2. PIP2 is involved in cell signaling, fx regulation of TRPs.

Glycerol-3-phosphate can be converted to lysophosphatidic acid, which can be converted to PA. Lipin (gene: LPIN) can convert PA to DAG.

Epigenetic changed genes in ME:

• DGKA (DGK-alpha) hypomethylated (2)
• DGKQ (DGK-theta) hypermethylated, with a negative foldchange (3)
• LPIN1 hypermethylated (2)

References:

1. Germain et al: Metabolic profiling of a ME/CFS discovery cohort reveals disturbances in fatty acid and lipid metabolism. Mol. BioSyst. 2017, 13, 371
2. Vega et al. DNA methylation Modifications associated with CFS. Plos One, aug 2014, vol 9, Issue 8, e104757
3. Brenu et al: Methylation profile of CD4+ T cells in CFS/ME. J. Clin Cell Immunol 5, 228