Delayed Impact of 2-Oxoadipate Dehydrogenase Inhibition on the Rat Brain Metabolism Is Linked to Protein Glutarylation.

ABSTRACT:

Background

The DHTKD1-encoded 2-oxoadipate dehydrogenase (OADH) oxidizes 2-oxoadipate-a common intermediate of the lysine and tryptophan catabolism. The mostly low and cell-specific flux through these pathways, and similar activities of OADH and ubiquitously expressed 2-oxoglutarate dehydrogenase (OGDH), agree with often asymptomatic phenotypes of heterozygous mutations in the DHTKD1 gene. Nevertheless, OADH/DHTKD1 are linked to impaired insulin sensitivity, cardiovascular disease risks, and Charcot-Marie-Tooth neuropathy. We hypothesize that systemic significance of OADH relies on its generation of glutaryl residues for protein glutarylation. Using pharmacological inhibition of OADH and the animal model of spinal cord injury (SCI), we explore this hypothesis.<

SUBMITTER: Boyko AI 

PROVIDER: S-EPMC9198357 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature