GCDH (F2P2M) Rabbit Monoclonal Antibody #43365

Glutaryl-CoA dehydrogenase (GCDH) is a mitochondria matrix enzyme that plays a role in the degradative pathway of lysine, hydroxylysine, and tryptophan by converting glutaryl-CoA to crotonyl-CoA (reviewed in 1). Crotonyl-CoA is further metabolized to acetyl-CoA, which enters the tricarboxylic acid (TCA) cycle for energy production. Mutation of the GCDH gene is the cause of glutamic aciduria type I (GAI), an autosomal recessive neurological disorder (2). GCDH deficiency leads to an accumulation of glutaryl-CoA and neurotoxic metabolites including glutaric acid and 3-hydroxyglutaric acid (3). Several studies have demonstrated the importance of GCDH in metabolic reprogramming in cancer. Melanoma cells can develop a dependency on GCDH (4). Mechanistically, loss of GCDH results in increased glutarylation of NRF2, a master transcriptional regulator of stress response genes associated with oxidative and metabolic stress responses, which results in increased NRF2 stability and activity and promotes cell death. Glioblastoma stem cells reprogram lysine catabolism, including upregulation of GCDH, which leads to an increase in histone crotonylation regulating tumor immunity (5). In contrast, in hepatocellular carcinoma (HCC), GCDH suppresses tumor growth and metastasis (6).