CPS1 Antibodies

Structure of CPS1

CPS1 is a mitochondrial enzyme with a molecular weight of approximately 165 kDa. Its precise molecular weight may vary slightly due to post-transcriptional modifications and subtype differences among different species.

This enzyme is composed of approximately 1,500 amino acids, forming a typical multi-domain spatial conformation. The tertiary structure of CPS1 consists of the synthase domain and the lyase domain, which are connected through intramolecular tunnels to achieve substrate channel effects. Its active center contains key ATP binding sites and carbamoyl phosphate synthesis sites. The N-acetylglutamate binding domain regulates enzyme activity by inducing conformational changes, and this allosteric regulation mechanism is crucial for maintaining the homeostasis of the urea cycle.

Fig. 1 Structural basis of CPS1 function and defects.¹

Key structural properties of CPS1:

• Multi-domain spatial conformation, containing synthetase and lyase dual functional regions
• Intramolecular ammonia channels enable efficient substrate transfer
• N-acetyl glutamic acid combined with domain by allosteric regulation control enzyme activity

Functions of CPS1

The main function of CPS1 is to catalyze the first step of ammonia detoxification in the liver urea cycle. In addition, this enzyme is also involved in the regulation of various physiological and pathological processes.

Unlike the synergistic action of subsequent enzymes in the urea cycle, CPS1 alone undertakes the rate-limiting step, and its activity is specifically activated by N-acetylglutamic acid. This allosteric regulatory mechanism ensures an accurate match between the ammonia detoxification process and metabolic requirements.

Applications of CPS1 and CPS1 Antibody in Literature

1. Ouyang, Shen‐Xi, et al. "Gasdermin‐E‐Dependent Non‐Canonical Pyroptosis Promotes Drug‐Induced Liver Failure by Promoting CPS1 deISGylation and Degradation." Advanced Science 11.16 (2024): 2305715. https://doi.org/10.1002/advs.202305715

This study reveals that in acetaminophen liver injury, GSDME mediates the deisG modification of CPS1 protein, promoting its K48 ubiquitination degradation and leading to ammonia metabolism disorders. Inhibiting GSDME can protect the function of CPS1 and reduce ammonia accumulation, providing a new target for treatment.

2. Sun, Xiao-Meng, et al. "CPS1 augments hepatic glucagon response through CaMKII/FOXO1 pathway." Frontiers in Pharmacology 15 (2024): 1437738. https://doi.org/10.3389/fphar.2024.1437738

Research has found that CPS1, the rate-limiting enzyme of the urea cycle, is a key molecule mediating glucagon-induced hepatic gluconeogenesis and elevated blood glucose. CPS1 enhances gluconeogenesis by triggering the release of calcium ions from the endoplasmic reticulum and activating the CaMKII-FOXO1 signaling pathway. The natural compound silymarin extracted from artichokes can be used as a CPS1 inhibitor, providing a new idea for the treatment of diabetes.

3. Owusu-Ansah, Melissa, et al. "NAGS, CPS1, and SLC25A13 (citrin) at the crossroads of arginine and pyrimidines metabolism in tumor cells." International Journal of Molecular Sciences 24.7 (2023): 6754. https://doi.org/10.3390/ijms24076754

Research has found that in various tumors such as glioblastoma and gastric cancer, the gene expression of the urea cycle rate-limiting enzyme CPS1 and the proteins required for its activation abnormally increases. This overexpression may drive the rapid proliferation of tumor cells by enhancing the activity of CAD complexes and promoting pyrimidine synthesis. The regulation of CPS1 activity in tumors may have a unique mechanism that does not rely on classical activators.

4. Wang, Shangyu, et al. "Clinical and genetic analysis of a case of late onset carbamoyl phosphate synthase I deficiency caused by CPS1 mutation and literature review." BMC Medical Genomics 16.1 (2023): 145. https://doi.org/10.1186/s12920-023-01569-w

This study reports a rare case of CPS1 deficiency that occurred during adolescence. The patient was misdiagnosed due to atypical clinical manifestations. Genetic testing revealed compound heterozygous mutations in the CPS1 gene, including a missense mutation and an unreported non-frameshift deletion mutation. This study provides an important reference for the early diagnosis and genotype-phenotype association of late-onset CPS1 deficiency.

5. Soria, Leandro R., et al. "O-GlcNAcylation enhances CPS1 catalytic efficiency for ammonia and promotes ureagenesis." Nature Communications 13.1 (2022): 5212. https://doi.org/10.1038/s41467-022-32904-x

This study reveals that hyperammonemia drives the O-GlcNAc glycosylation modification of the CPS1 enzyme by increasing the UDP-GlcNAc level in the liver. This modification directly enhances the catalytic efficiency of CPS1 for ammonia, thereby strengthening the generation of urea and the detoxification ability of ammonia. Inhibiting O-GlcNAc hydrolase can effectively reduce blood ammonia, providing a new target for the treatment of hyperammonemia.

Creative Biolabs: CPS1 Antibodies for Research

Creative Biolabs specializes in the production of high-quality CPS1 antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

• Custom CPS1 Antibody Development: Tailor-made solutions to meet specific research requirements.
• Bulk Production: Large-scale antibody manufacturing for industry partners.
• Technical Support: Expert consultation for protocol optimization and troubleshooting.
• Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our CPS1 antibodies, custom preparations, or technical support, contact us at email.