Carboxypeptidases in disease: Insights from peptidomic studies

Matthew R. Sapio, Lloyd D. Fricker

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Carboxypeptidases (CPs) perform many diverse physiological functions by removing C-terminal amino acids from proteins and peptides. Some CPs function in the degradation of proteins in the digestive tract while other enzymes play biosynthetic roles in the formation of neuropeptides and peptide hormones. Another set of CPs modify tubulin by removing amino acids from the C-terminus and from polyglutamyl side chains, thereby altering the properties of microtubules. This review focuses on three CPs: carboxypeptidase E, carboxypeptidase A6, and cytosolic carboxypeptidase 1. Naturally occurring mutations in all three of these enzymes are associated with disease phenotypes, ranging from obesity to epilepsy to neurodegeneration. Peptidomics is a useful tool to investigate the relationship between these mutations and alterations in peptide levels. This technique has also been used to define the function and characteristics of CPs. Results from peptidomics studies have helped to elucidate the function of CPs and clarify the biological underpinnings of pathologies by identifying peptides altered in disease states. This review describes the use of peptidomic techniques to gain insights into the normal function of CPs and the molecular defects caused by mutations in the enzymes.

Original languageEnglish (US)
Pages (from-to)327-337
Number of pages11
JournalProteomics - Clinical Applications
Volume8
Issue number5-6
DOIs
StatePublished - 2014

Fingerprint

Carboxypeptidases
Mutation
Carboxypeptidase H
Enzymes
Amino Acids, Peptides, and Proteins
Peptides
Peptide Hormones
Pathology
Neuropeptides
Microtubules
Proteolysis
Gastrointestinal Tract
Epilepsy
Obesity
Phenotype
Amino Acids
Degradation
Defects

Keywords

  • Carboxypeptidase
  • Metallopeptidase

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Medicine(all)

Cite this

Carboxypeptidases in disease : Insights from peptidomic studies. / Sapio, Matthew R.; Fricker, Lloyd D.

In: Proteomics - Clinical Applications, Vol. 8, No. 5-6, 2014, p. 327-337.

Research output: Contribution to journalArticle

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