ALDH4A1 and ME

Delta-1-pyrroline-5-carboxylate dehydrogenase, mitochondrial is an enzyme that in humans is encoded by the ALDH4A1 gene (aldehyde dehydrogenase 4 family, member A1). This enzyme is a mitochondrial matrix NAD-dependent dehydrogenase that catalyzes the second step of the proline degradation pathway, converting pyrroline-5-carboxylate to glutamate. Deficiency of this enzyme is associated with type II hyperprolinemia, an autosomal recessive disorder characterized by accumulation of delta-1-pyrroline-5-carboxylate (P5C) and proline. (1).

Pyrroline-5-carboxylic acid is increased in ME patients (2).

The gene ALDH4A1 has been found epigenetic changed (hypermethylated) in ME (3).

Expression of the proteins P5C-dehyrogenase and P5C-synthase have been found upregulated in ME (4).

P5C-dehydrogenase has been found to be an immunoreactive protein against IgGs from POTS-patients (5).

References:

1. Wikipedia: Aldehyde dehydrogenase 4 family, member A1
2. Naviaux et al: Metabolic features of CFS. www.pnas.org/cgi/doi/10.1073/pnas.1607571113
3. Vega et al. DNA methylation Modifications associated with CFS. Plos One, aug 2014, vol 9, Issue 8, e10475
4. Ciregia et al.
   Translational Psychiatry (2016), 6, e904
   doi:10.1038/tp.2016.184
5. Wang et al: Autoimmunoreactive IgGs from patients with POTS. Prot. Clin. Appl. 2012, 6, 1-11.