Proteolytic and Cellular Mechanisms in Prohormone Processing

215 pages, 34 figures, 20 tables, hardcover This text is designed to provide the reader with an understanding of current knowledge concerning proteases involved in prohormone processing, and cellular aspects that must be considered for proper processing, storage, and secretion of bioactive peptides. Cellular aspects of the targeting and activation of peptide hormones in the secretory pathway are discussed in the first two chapters. The next chapters (chapters 2-6) discuss the endoproteases that are involved in prohormone processing, including the subtilisin/kexin of prohormone convertases, a novel cysteine protease known as prohormone thiol protease (PTP), and an aspartyl protease that has been termed POMC converting enzyme (PCE). Subsequent to the actions of endoproteases, carboxypeptidase and aminopeptidase enzymes (chapter 7) that remove basic amino acids from the COOH- and NH2-termini of peptide intermediates are needed. Moreover, recent molecular genetic studies illustrate the role of prohormone conv! ertases 1 and 2, as well as the carboxypeptidase E/H, processing enzymes in obesity and conditions related to diabetes. Regulation of processing proteases by the 7B2 polypeptide as a chaperone and inhibitor is presented, as well as a potential role for a family of a1-antichymotrypsin protease inhibitors. Subsequent to secretion, extracellular proteolysis of neuropeptides and peptide activation of specific receptors is discussed.