Generation of methionine and leucine-enkephalin from precursor molecules by cation-sensitive neutral endopeptidase of bovine pituitary

Highly purified preparations of cation-sensitive neutral endopeptidase, from bovine pituitary, and also rabbit brain, generate methionine-enkephalin, from α-endorphin, a peptide containing the amino acid sequence 61-76 of β-lipotropin (β-LPH),^{{black star}} {black star} Abbreviations: β-Lipotropin, β-LPH; 2NA, 2-naphthylamide; Tyr-Gly-Gly-Phe-Leu-Thr-2NA, Leu-enkephalin-Thr-2NA; N-Benzyloxycarbonyl-Tyr-Gly-Gly-Phe-Leu-Thr-2NA, Z-Leu-enkephalin-Thr-2NA; pNA, p-nitroanilide; HPLC, high performance liquid chromatography; Bz, α-N-Benzoyl. The enzyme also catalyzes the hydrolysis of the Leu-Thr bond in the synthetic peptide Tyr-Gly-Gly-Phe-Leu-Thr-2-naphthylamide with the release of leucine-enkephalin and Thr-2-naphthylamide. Neither Met- nor Leu-enkephalin are degraded. The data indicate that the presence of a free N-terminal group of tyrosine inhibits the further degradation of Leu- and Met-enkephalin by the endopeptidase. It is suggested that cation-sensitive neutral endopeptidase is one of the enzymes capable of generating Met- and Leu-enkephalin in, vivo.