Genetic, structural and biochemical basis of carbamoyl phosphate synthetase 1 deficiency
Abstract
Carbamoyl phosphate synthetase 1 (CPS1) plays a paramount role in liver ureagenesis since it catalyzes the first and rate-limiting step of the urea cycle, the major pathway for nitrogen disposal in humans. CPS1 deficiency (CPS1D) is an autosomal recessive inborn error which leads to hyperammonemia due to mutations in the CPS1 gene, or is caused secondarily by lack of its allosteric activator NAG. Proteolytic, immunological and structural data indicate that human CPS1 resembles Escherichia coli CPS in structure, and a 3D model of CPS1 has been presented for elucidating the pathogenic role of missense mutations. Recent availability of CPS1 expression systems also can provide valuable tools for structure-function analysis and pathogenicity-testing of mutations in CPS1. In this paper, we provide a comprehensive compilation of clinical CPS1 mutations, and discuss how structural knowledge of CPS enzymes in combination with in vitro analyses can be a useful tool for diagnosis of CPS1D.
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CPS1 converts ammonia to carbamoyl phosphate to enter the urea cycle.
“CPS1 (Carbamoyl phosphate synthetase I) is responsible for converting ammonia to carbamoyl phosphate to enter the urea cycle35”
From Spatial transcriptomics of healthy and fibrotic human liver at single-cell resolution (2025) · cites this paper as [35]
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SIRT5 deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle
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Spatial transcriptomics of healthy and fibrotic human liver at single-cell resolution
Watson, B. R., Paul, B., Rahman, R. U., Amir-Zilberstein, L., Segerstolpe, Å., Epstein, E. T., Murphy, S., Geistlinger, L., Lee, T., Shih, A., et al. (2025) · Nature Communications · doi:10.1038/s41467-024-55325-4 · Cited by 123 · see citing works
Ghanem, S. S., Al-Barazenji, T., Badi, R., & Abdelalim, E. M. (2026) · Molecular Biology Reports · doi:10.1007/s11033-026-12480-9
- Authors
- Martínez, A. I., Pérez-Arellano, I., Pekkala, S., Barcelona, B., & Cervera, J.
- Affiliations
- Centro de Investigacion Principe Felipe (ES)
- Instituto de Salud Carlos III (ES)
- Corresponding author
- Cervera, Javier
- Venue
- Molecular Genetics and Metabolism
- Publisher
- Elsevier BV
- Published
- 2010-12
- Volume
- 101
- Issue
- 4
- Pages
- 311-323
- ISSN
- 1096-7192 (ISSN-L)
- OpenAlex
- W2056878318
- Cited by
- 67
- References
- 3
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 3 · 2023: 5 · 2022: 3 · 2021: 5 · 2020: 2 · 2019: 6 · 2018: 3 · 2017: 6 · 2016: 5 · 2015: 9 · 2014: 6 · 2013: 3 · 2012: 2
- FWCI
- 0.23
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Molecular Genetics and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- CPS1, urea cycle disorders, hyperammonemia, inborn errors of metabolism, missense mutations, N-acetylglutamate, allosteric activation, protein structure-function relationship, nitrogen metabolism
- MeSH terms
- Carbamoyl-Phosphate Synthase (Ammonia), Humans, Protein Structure, Tertiary, Carbamoyl-Phosphate Synthase I Deficiency Disease, Urea Cycle Disorders, Inborn
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