Biodegradation of alpha-MSH and derived peptides by rat brain extracts, and by rat and human serum.
The peptides alpha-MSH and MSH/ACTH 4-10 were degraded by rat brain extracts and serum to yield free amino acids among the end-products. Breakdown of these two peptides was double that of a related synthetic hexapeptide Met (0)-Glu-His-Phe-D-Lys-Phe. No significant breakdown of the hexapeptide occurred after incubation with human serum; it also had almost negligible pigmentary effects in vivo and in vitro when compared to alpha-MSH. The patterns of amino acid release indicate possible endopeptidase cleavage at Phe-Arg in alpha-MSH followed by secondary exopeptidase action to release free amino acids. For the hexapeptide, the primary cleavage point occurred at the -His3-Phe4 bond. The stability of this analog in human sera, coupled with its lower rate of degradation in the CNS, may contribute to its more potent behavioral actions in vivo.
D000324:Adrenocorticotropic Hormone / Q000378:metabolism; D000818:Animals; D001673:Biodegradation, Environmental; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D009074:Melanocyte-Stimulating Hormones / Q000031:analogs & derivatives / Q000097:blood / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship; D013997:Time Factors
D010455:Peptides; D000324:Adrenocorticotropic Hormone; D009074:Melanocyte-Stimulating Hormones