Divergent Induction of Branched-Chain Aminotransferases and Phosphorylation of Branched Chain Keto-Acid Dehydrogenase Is a Potential Mechanism Coupling Branched-Chain Keto-Acid-Mediated-Astrocyte Activation to Branched-Chain Amino Acid Depletion-Mediated Cognitive Deficit after Traumatic Brain Injury.

ABSTRACT: Deficient branched-chain amino acids (BCAAs) are implicated in cognitive dysfunction after traumatic brain injury (TBI). The mechanism remains unknown. BCAAs are catabolized by neuron-specific cytosolic and astrocyte-specific mitochondrial branched-chain aminotransferases (BCATc, BCATm) to generate glutamate and branched-chain keto-acids (BCKAs) that are metabolized by the mitochondrial branched-chain keto-acid dehydrogenase (BCKD) whose activity is regulated by its phosphorylation state. BCKD phosphorylation by BCKD kinase (BCKDK) inactivates BCKD and cause neurocognitive dysfunction, whereas dephosphorylation by specific phosphatase restores BCKD activity. Real-time polymerase chain reaction showed rapidly and significantly decreased BCATc messenger RNA (mRNA) levels, but significantly i

SUBMITTER: Xing G 

PROVIDER: S-EPMC6196747 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature