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Normal Function
The PEPD gene provides instructions for making the enzyme prolidase, also called peptidase D. Prolidase helps divide certain dipeptides, which are molecules composed of two protein building blocks (amino acids). Specifically, prolidase divides dipeptides containing the amino acids proline or hydroxyproline. By freeing these amino acids, prolidase helps make them available for use in producing proteins that the body needs.
Prolidase is also involved in the final step of the breakdown of some proteins obtained though the diet and proteins that are no longer needed in the body. Prolidase is particularly important in the breakdown of collagens, a family of proteins that are rich in proline and hydroxyproline. Collagens are an important part of the extracellular matrix, which is the lattice of proteins and other molecules outside the cell. The extracellular matrix strengthens and supports connective tissues, such as skin, bone, cartilage, tendons, and ligaments. Collagen breakdown occurs during the maintenance (remodeling) of the extracellular matrix.
Health Conditions Related to Genetic Changes
Prolidase deficiency
At least 19 mutations in the PEPD gene have been identified in people with prolidase deficiency, a disorder with a wide variety of signs and symptoms including skin problems and intellectual disability. The PEPD gene mutations identified in people with prolidase deficiency result in the loss of prolidase enzyme activity.
It is not well understood how the absence of prolidase activity results in the various signs and symptoms of prolidase deficiency. Researchers have suggested that accumulation of dipeptides that have not been broken down may lead to cell death. When cells die, their contents are released into the surrounding tissue, which could cause inflammation and lead to the skin problems seen in prolidase deficiency. Impaired collagen breakdown during remodeling of the extracellular matrix may also contribute to the skin problems. The intellectual disability that occurs in prolidase deficiency might result from problems in processing neuropeptides, which are brain signaling proteins that are rich in proline. It is unclear how absence of prolidase activity results in the other features of prolidase deficiency.
More About This Health ConditionOther Names for This Gene
- aminoacyl-L-proline hydrolase
- imidodipeptidase
- MGC10905
- PEPD_HUMAN
- PROLIDASE
- proline dipeptidase
- X-Pro dipeptidase
- xaa-Pro dipeptidase
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Falik-Zaccai TC, Khayat M, Luder A, Frenkel P, Magen D, Brik R, Gershoni-Baruch R, Mandel H. A broad spectrum of developmental delay in a large cohort of prolidase deficiency patients demonstrates marked interfamilial and intrafamilial phenotypic variability. Am J Med Genet B Neuropsychiatr Genet. 2010 Jan 5;153B(1):46-56. doi: 10.1002/ajmg.b.30945. Citation on PubMed
- Forlino A, Lupi A, Vaghi P, Icaro Cornaglia A, Calligaro A, Campari E, Cetta G. Mutation analysis of five new patients affected by prolidase deficiency: the lack of enzyme activity causes necrosis-like cell death in cultured fibroblasts. Hum Genet. 2002 Oct;111(4-5):314-22. doi: 10.1007/s00439-002-0792-5. Epub 2002 Aug 14. Citation on PubMed
- Lupi A, De Riso A, Torre SD, Rossi A, Campari E, Vilarinho L, Cetta G, Forlino A. Characterization of a new PEPD allele causing prolidase deficiency in two unrelated patients: natural-occurrent mutations as a tool to investigate structure-function relationship. J Hum Genet. 2004;49(9):500-506. doi: 10.1007/s10038-004-0180-1. Epub 2004 Aug 11. Citation on PubMed
- Lupi A, Rossi A, Campari E, Pecora F, Lund AM, Elcioglu NH, Gultepe M, Di Rocco M, Cetta G, Forlino A. Molecular characterisation of six patients with prolidase deficiency: identification of the first small duplication in the prolidase gene and of a mutation generating symptomatic and asymptomatic outcomes within the same family. J Med Genet. 2006 Dec;43(12):e58. doi: 10.1136/jmg.2006.043315. Citation on PubMed or Free article on PubMed Central
- Lupi A, Tenni R, Rossi A, Cetta G, Forlino A. Human prolidase and prolidase deficiency: an overview on the characterization of the enzyme involved in proline recycling and on the effects of its mutations. Amino Acids. 2008 Nov;35(4):739-52. doi: 10.1007/s00726-008-0055-4. Epub 2008 Mar 14. Citation on PubMed
- Mitsubuchi H, Nakamura K, Matsumoto S, Endo F. Inborn errors of proline metabolism. J Nutr. 2008 Oct;138(10):2016S-2020S. doi: 10.1093/jn/138.10.2016S. Citation on PubMed
- Surazynski A, Donald SP, Cooper SK, Whiteside MA, Salnikow K, Liu Y, Phang JM. Extracellular matrix and HIF-1 signaling: the role of prolidase. Int J Cancer. 2008 Mar 15;122(6):1435-40. doi: 10.1002/ijc.23263. Citation on PubMed
- Wang H, Kurien BT, Lundgren D, Patel NC, Kaufman KM, Miller DL, Porter AC, D'Souza A, Nye L, Tumbush J, Hupertz V, Kerr DS, Kurono S, Matsumoto H, Scofield RH. A nonsense mutation of PEPD in four Amish children with prolidase deficiency. Am J Med Genet A. 2006 Mar 15;140(6):580-5. doi: 10.1002/ajmg.a.31134. Citation on PubMed
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