ACAD8 and ME

Fluge, Mella et al. have shown that ME is associated with defective oxidative metabolism - most likely involving impaired pyruvate dehydrogenase function - leading to increased utilization  of ketogenic amino acids to fuel the TCA-cycle (1).

A proteomic study on cerebrospinal fluid from ME/CFS patients has shown an upregulation of the pathway "valine, leucine and isoleucine degradation" (table S6 in ref 2).

The gene acyl-CoA.dehydrogenase family member 8 (ACAD8) has been found epigenetic changed (hypermethylated) in ME (3).

ACAD8 is an isobutyryl-CoA dehydrogenase that functions in the catabolism of branched-chain amino acids including valine, and shows high reactivity toward isobutyryl-CoA. ACAD8 is responsible for the third step in the breakdown of valine and converts isobutyryl-CoA into methylacrylyl-CoA.

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. Schutzer et al: Distinct Cerebrospinal Fluid Proteomes Differentiate Post- Treatment Lyme Disease from Chronic Fatigue Syndrome. PLOS One February 2011, volume 6, Issue 2
3. Vega et al. DNA methylation Modifications associated with CFS. Plos One, aug 2014, vol 9, Issue 8, e104757
4. Wikipedia: ACAD8