产品描述:
Branched-chain amino acid transferases (BCATs) catalyze reversible transamination of leucine, isoleucine, and valine branched-chain amino acids to their respective α-keto acids, liberating L-glutamate.{20159,20160} Two forms of BCAT are present in mammals. Mitochondrial BCAT (BCATm) exists in most tissues throughout the body, whereas cytosolic BCAT (BCATc) is confined to the brain, where it regulates glutamate synthesis for release during neuronal excitation. Thus, BCATc inhibition may be useful for the treatment of neurodegenerative and behavioral disorders involving disturbances of the glutamatergic system. BCATc inhibitor 2 is a sulfonyl hydrazide that inhibits BCATc (IC50s = 0.81 and 0.2 µM for human and rat, respectively) with 15-fold selectivity over BCATm.{27460,27458,27459} This compound has been shown to block calcium influx into neurons (IC50 = 4.8 µM) following inhibition of glutamate uptake and to demonstrate neuroprotective efficacy in an in vivo rat model of neurodegeneration.{27458}