Neuropeptide biosynthesis: focus on the carboxypeptidase processing enzyme

Abstract

Many peptide neurotransmitters and hormones are initially synthesized as large protein precursors (prohormones) which must undergo proteolytic processing to yield the biologically active fragment. Often, the neurotransmitter or hormone is flanked by pairs of basic amino acids in the precursor molecule, and the sequential action of a trypsin-like endopeptidase followed by a carboxypeptidase-B-like exopeptidase would liberate the hormone. An important question is whether unique enzymes are associated with each prohormone, or whether general processing enzymes perform similar cleavages for all prohormones. Recent studies on the carboxypeptidase-B-like processing enzyme associated with enkephalin biosynthesis suggests that this enzyme is also involved in the biosynthesis of many other peptide hormones and neurotransmitters.