GPD2, the glycerophosphate-shuttle and ME

Glucose/pyruvate and lipid metabolism have been found dysregulated in ME (1, 2, 3)

Glycero-3-phosphate has been found up-regulated in ME (3).

The gene GPD2 codes mithochondrial glycerol-3-phosphate dehydrogenase (mGPDH).

mGPDH oxidizes glycerol-3-phosphate to dihydroxyacetone phosphate.

mGPDH is a very important enzyme of intermediary metabolism and as a component of glycerophosphate shuttle at the crossroads of glycolysis, oxidative phosphorylation and fatty acid metabolism (4).

These genes have been found epigenetic changed (hypermethylated) in ME (5):

• GPD2, glycerol-3-phosphate dehydrogenase 2
• SLC37A3, solute carrier family 37, glycerol-3-phosphate transporter
• DAK, dihydroxyacetone kinase 2 homolog

References:

1. Fluge et al: Metabolic profiling indicates impaired pyruvate dehydrogenase function in myalgic encephalopathy / chronic fatigue syndrome. JCI Insight. 2016; 1(21):e89376. Doi 10.1172/jci.insight.89276
2. Naviaux et al: Metabolic features of CFS. www.pnas.org/cgi/doi/10.1073/pnas.1607571113
3. Germain et al: Metabolic profiling of a ME/CFS discovery cohort reveals disturbances in fatty acid and lipid metabolism. Mol. BioSyst. 2017, 13, 371
4. Mracek et al: The function and the role of the mitochondrial glycerol-3-phosphate dehydrogenase in mammalian tissue. Biochimica et Biophysica Acta 1827, 2013, 401-410.
5. Vega et al. DNA methylation Modifications associated with CFS. Plos One, aug 2014, vol 9, Issue 8, e104757