Proteolytic conversion of beta-endorphin by brain synaptic membranes. Characterization of generated beta-endorphin fragments and proposed metabolic pathway.
This study concerned the fragmentation of beta-endorphin (beta-EP-(1-31) by synaptic membrane-bound peptidases. The peptides which accumulated during digestion of beta-endorphin by isolated synaptosomal plasma membrane preparations of rat brain were separated and isolated by high pressure liquid chromatography. Amino acid analysis of the peptide fractions indicated the formation of beta-EP-(1-21), beta-EP-(2-21) (pH 7.4), beta-EP-(18-31), beta-EP-(1-14), and beta-EP-(1-13) (pH 5.0) in addition to previously identified gamma-endorphin (beta-EP-(1-17)), alpha-endorphin (beta-EP-(1-16), and their des-tyrosine fragments (Burbach, J. P. H., Loeber, J. G., Verhoef, J., Wiegant, V. M., De Kloet, E. R., and De Wied, D. (1980) Nature 283, 96-97). The beta-endorphin fragments obtained with crude or with purified synaptosomal plasma membranes differed only quantitatively. The peptidase which converted gamma-endorphin into beta-EP-(1-16), beta-EP-(1-15), beta-EP-(1-14), and beta-EP-(1-13), was considerably active at pH 5.0 and resembled carboxypeptidase A in degrading gamma-endorphin; the activity was reduced by the carboxypeptidase A inhibitor D-phenylalanine. The data supplement previous findings and allow routes to be delineated for the conversion of beta-endorphin by brain synaptic membranes. A pathway comprising the main events in the conversion processes is proposed and is discussed in relationship to the significance of beta-endorphin as a precursor for neuropeptides with distinct central activities.
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004723:Endorphins / Q000378:metabolism*; D006801:Humans; D008297:Male; D010446:Peptide Fragments / Q000032:analysis; D010649:Phenylalanine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013570:Synaptic Membranes / Q000378:metabolism* / Q000648:ultrastructure; D013574:Synaptosomes / Q000378:metabolism; D001615:beta-Endorphin
D004723:Endorphins; D010446:Peptide Fragments; D010649:Phenylalanine; D001615:beta-Endorphin