Adrenocorticotropin: ACTH1-38 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 ACTH1-39 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 ACTH1-39 remaining and products formed. Time- and enzyme-dependent disappearance of ACTH1-39 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 ACTH1-38. These results indicate the predominance of carboxypeptidase activity in the degradation of ACTH1-39 by brain synaptic membranes.