Formation of biologically active peptides.
Many small biologicaly active peptides are derived from larger precursor forms which fulfil a variety of roles in the synthesis, segregation and intracellular migration of secretory products. Limited proteolysis may occur at several stages during this process, giving rise to products that are either degraded (e.g. the prepeptides) or discharged coordinately from their cells of origin during exocytosis (e.g. insulin and C-peptide). Molecular defects have recently been found to occur at cleavage sites in proinsulin as well as in other proproteins, and these point mutations may, in some instances, be responsible for familial metabolic disorders. The nature and cell specificity of the proteolytic enzymes involved in the conversion of the various precursor forms remains unresolved. Recent studies in our laboratory have led to the identification of precursors of glucagon and somatostatin in rat islets of Langerhans. Analysis of tryptic maps of these precursors has shown that a trypsin-like enzyme would be sufficient to cleave the C-terminally located somatostatin sequence from its precursor (relative molecular mass 12,500), but that both trypsin-like and carboxypeptidase B-like enzymes would be necessary to cleave the internal glucagon sequence from its prohormone (relative molecular mass 18,000). Molecular cloning techniques have provided valuable new approaches to analysing the structures of a variety of precursor forms, including those for insulin, gastrin, growth hormone, adrenocorticotropic hormone and the endorphins, and in the future will undoubtedly shed more light on the structures of their chromosomal genes, the mechanisms regulating their expression, and their evolutionary origins.
D000595:Amino Acid Sequence; D005934:Glucagon / Q000096:biosynthesis; D006728:Hormones / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism; D008970:Molecular Weight; D010447:Peptide Hydrolases / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D013004:Somatostatin / Q000096:biosynthesis
D006728:Hormones; D010455:Peptides; D011498:Protein Precursors; D011506:Proteins; D013004:Somatostatin; D005934:Glucagon; D010447:Peptide Hydrolases