Carboxypeptidase E

Carboxypeptidase E (CPE) is an enzyme that plays a crucial role in the processing and regulation of peptide hormones and neuropeptides. It is primarily found in the secretory pathway of cells, particularly in the trans-Golgi network and secretory vesicles. CPE is involved in the cleavage of C-terminal basic amino acids from peptide precursors, leading to the production of biologically active peptides.

Function

Carboxypeptidase E is responsible for the post-translational processing of prohormones and neuropeptides. It specifically cleaves C-terminal basic amino acids, such as arginine and lysine, from peptide precursors. This cleavage step is essential for the generation of active peptides that regulate various physiological processes, including neurotransmission, hormone secretion, and appetite regulation.

Structure

Carboxypeptidase E is a zinc metalloenzyme, meaning it requires zinc ions for its catalytic activity. It consists of a single polypeptide chain with a molecular weight of approximately 74 kDa. The enzyme contains several functional domains, including a signal peptide for targeting to the secretory pathway, a propeptide region that is involved in enzyme activation, and a catalytic domain responsible for substrate cleavage.

Role in Peptide Processing

Carboxypeptidase E is involved in the processing of a wide range of peptide precursors. It acts on prohormones, which are inactive peptide precursors synthesized in the endoplasmic reticulum. After synthesis, prohormones are transported to the Golgi apparatus, where they undergo various post-translational modifications, including proteolytic cleavage by carboxypeptidase E. This cleavage step is crucial for the production of active peptides that can be packaged into secretory vesicles and released upon appropriate stimulation.

Clinical Significance

Mutations or deficiencies in carboxypeptidase E have been associated with various human diseases. For example, inactivating mutations in the CPE gene have been linked to a rare genetic disorder called carboxypeptidase E deficiency. This condition is characterized by impaired processing of peptide precursors, leading to the accumulation of inactive peptides and disrupted physiological functions. Carboxypeptidase E deficiency can manifest as neuroendocrine abnormalities, including obesity, diabetes, and neurological disorders.

See Also

• Prohormone
• Neuropeptide
• Zinc metalloenzyme
• Endoplasmic reticulum
• Golgi apparatus
• Secretory vesicles
• Carboxypeptidase E deficiency