Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is proposed that all peptide hormones and releasing factors are biosynthesized in the form of precursor molecules which are biologically inactive. Enzymic activation may take place by hydrolytic cleavage to release a terminal COOH group or by transmidation to form a COOH-terminal amide. Studies with pituitary prohormones and hormones are providing data that support this hypothesis. Evidence has been obtained that the 91 residue beta-lipotropin (beta-LPH) is the prohormone of beta-melanotropin (beta-MSH). The specificity of the pituitary enzymes involved in release of the hormone was demonstrated by the isolation of five constituent fragments of LPH, which were obtained in homogeneous form from the pituitary gland of the pig. The enzymes have specificities similar to trypsin and carboxypeptidase B; carboxypeptidase A and aminopeptidase activities do not appear to be involved. Mild digestion of beta-LPH by trypsin in vitro has confirmed the susceptibility of the peptide bond on the carboxy side of the paired basic residues at positions 59 and 60, adjacent to the COOH-terminus of beta-MSH, and tryptic digestion of a model peptide demonstrated the same specificity. The paired basic residues at positions 39 and 40 adjacent to the NH2-terminus of beta-MSH were more resistant to tryptic attack, both in LPH and in a model peptide. In the gland it is apparent that LPH is cleaved on the carboxy side of the paired lysyl residues at positions 39 and 40, whereas in the synthetic peptide cleavage takes place in between these residues. The activating enzyme may differ from trypsin; alternatively, explanation may be found in the conformation of the prohormone. Prediction of secondary indicates that both pairs of basic residues lie adjacent to beta-bends on the surface of the molecule and occupy sites accessible to enzymic attack. It seems likely that alpha-MSH and corticotropin (ACTH) share a common pro hormone. The release of ACTH could involve cleavage of a -Gly-Ser- bond in the prohormone to expose the NH2-terminus of the hormone. With alpha-MSH, a concerted acetylation and cleavage may take place to form the N-acetylserine residue; the COOH-terminus may be released as an amide by direct transamidation of a -Val-Gly- bond in the prohormone. Release of either hormone would be accompanied by the release of contiguous fragments of the prohormone. We have isolated two novel polypeptides from pig pituitary in substantial quantity and have determined the primary structures. They may represent fragments of a prohormone to alpha-MSH or ACTH.
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PMID:Prohormones of beta-melanotropin (beta-melanocyte-stimulating hormone, beta-MSH) and corticotropin (adrenocorticotropic hormone, ACTH): structure and activation. 18 Dec 27

Melanin-concentrating hormone (MCH) is a cyclic peptide which behaves as an antagonist of the pituitary melanotropic hormone alpha-melanocyte-stimulating hormone in fishes. Cloning of the rat MCH cDNA precursor recently revealed the presence of an additional putative peptide named NEI. The present work examined the susceptibility of these novel peptides to hydrolysis by various purified exo- and endo-peptidases including endopeptidases 24.11 (NEP), 24.15, 24.16, angiotensin-converting enzyme, leucine aminopeptidase and carboxypeptidase A. NEP attacked MCH at three sites of the molecule with an apparent affinity of about 12 microM and a kcat. of 4 min-1. The first site of cleavage was at Cys-7-Met-8, i.e. within the peptide loop formed by the internal disulphide bridge. NEP could therefore be considered as an MCH-inactivating peptidase since the degradation products generated are probably devoid of biological activity. In contrast, NEI neither inhibited the degradation of the NEP chromogenic substrate glutaryl-Phe-Ala-Phe-p-aminobenzoate nor was susceptible to proteolysis by NEP. Unlike NEP, angiotensin-converting enzyme, endopeptidase 24.15 and endopeptidase 24.16 appeared totally unable to cleave MCH, whereas the peptide was readily degraded by aminopeptidase M and carboxypeptidase A.
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PMID:Hydrolysis of rat melanin-concentrating hormone by endopeptidase 24.11 (neutral endopeptidase). 152 Feb 71

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.
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PMID:Proteolytic conversion of beta-endorphin by brain synaptic membranes. Characterization of generated beta-endorphin fragments and proposed metabolic pathway. 627 86