Adrenocorticotropin: AdH1–38 Is a Major Product of Biotransformation by Brain Synaptic Membranes

: Since adrenocorticotropic hormone is found in the brain, and several of its fragments affect adaptive behavior, the formation of fragments of ACTH,1–39 by a rat brain synaptic membrane fraction was investigated. Following the incubations at physiological pH conditions, the digests were fractionated by HPLC to quantitate the amounts of ACTH,1–39 remaining and products formed. Time- and enzyme-dependent disappearance of ACTH,1–39 was accompanied by the accumulation of a major peptide metabolite (product B). Amino acid analysis and NH2--terminal end-group determination revealed that product B was identical to ACTH,1–38. These results indicate the predominance of carboxypeptidase activity in the degradation of ACTH 1–39 by brain synaptic membranes.