Carboxypeptidase E

Carboxypeptidase E (CPE) functions in the biosynthesis of numerous neuropeptides and peptide hormones in nearly all species, although it is not present in Drosophila which use the related enzyme carboxypeptidase D (CPD) as the sole neuropeptide-generating enzyme. Mammals also have CPD but it plays only a minor role in the production of most neuropeptides and peptide hormones. CPE is primarily expressed in neuroendocrine tissues where it is localized to peptide-containing secretory vesicles. The pH optimum of CPE is 5.0-5.5, which corresponds to the pH within secretory vesicles. Multiple forms of CPE have been detected that differ in proteolytic processing of the N-and/or C-terminus. Forms of CPE with a truncated C-terminus are soluble while those with a full-length C-terminus are peripherally bound to membranes at pH values of 5.0-6.0 but released from membranes at neutral pH. Both forms of CPE are cosecreted from cells along with peptides, although CPE is inactive at the neutral pH of the extracellular environment. CPE protein may have functions beyond its enzymatic activity, but this is controversial. Mice that lack CPE activity exhibit many physiological and behavioral abnormalities including obesity, impaired fertility, learning deficits, and elevated depressive-and anxiety-like behavior. A variety of human CPE gene mutations have been reported, including several that delete the majority of CPE protein. Patients homozygous for these severe CPE gene mutations exhibit morbid obesity and intellectual disabilities.