Molecular and Biochemical Features of the Mitochondrial Enzyme Ornithine Transcarbamylase: A Possible New Role as a Signaling Factor

Dı́az-Muñoz, Mauricio; Hernández‐Muñoz, Rolando

doi:10.2174/092986710791331031

Cited by 12 publications

(8 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4). OTC, a one‐carbon‐unit transferring enzyme that synthesizes citrulline using ornithine and carbamoylphosphate as substrates, is expressed in a large variety of organisms, from bacteria to mammals 59. Inborn errors associated with a deficiency of OTC activity cause mainly urea cycle‐related disorders, and lead to hyperammonemic states, which may become lethal.…”

Section: Discussionmentioning

confidence: 99%

Comparative hepatic proteome analysis between lean and obese rats fed a high‐fat diet reveals the existence of gender differences

Wang

Choi

et al. 2012

Proteomics

View full text Add to dashboard Cite

Gender differences in obesity stem from metabolic and hormonal differences between sexes and contribute to differences between women and men in health risks attributable to obesity. We hypothesized that liver may be an ideal target for the evaluation of gender differences in obesity development in response to a high-fat diet (HFD). Therefore, to test this hypothesis, we performed a global proteome analysis in the liver of lean and obese rats of both genders who were fed an HFD through 2-DE combined with MALDI-TOF-MS. When rats were exposed to HFD, male rats gained more body weight with increased values of plasma biochemical parameters than female rats. Image analysis and further statistical analysis of a 2-DE protein map allowed for the detection and identification of 34 proteins that were significantly modulated in a gender-dependent manner. We found 19 proteins showing identical gender-different regulation in both normal diet (ND) and HFD. Five proteins also showed clear gender differences in both ND and HFD; however, their regulation modes in HFD were opposite to those in ND. Of particular interest, 10 proteins showed gender differences only in either ND or HFD rats. Present proteomic insight into gender-dimorphic protein modulation in liver would aid in the improvement of gender awareness in the health-care system and in implementation of evidence-based gender-specific clinical recommendations.

show abstract

Section: Discussionmentioning

confidence: 99%

Comparative hepatic proteome analysis between lean and obese rats fed a high‐fat diet reveals the existence of gender differences

Wang

Choi

et al. 2012

Proteomics

View full text Add to dashboard Cite

show abstract

“…It is formed by two distinct structural domains that surround a deep cleft, linked by two long interdomain helices (h5 and h12; Figure 2B). Both structural domains have an αβα-topology, basically consisting of a central 5-stranded parallel β-sheet with α-helices on both sides (Shi et al, 2000;Diaz-Munoz and Hernandez-Munoz, 2010). Each subunit contains one active site situated at the hinge between its two domains.…”

Section: Protein Maturation Targeting and Secondary Modificationmentioning

confidence: 99%

Ornithine Transcarbamylase – From Structure to Metabolism: An Update

et al. 2021

View full text Add to dashboard Cite

Ornithine transcarbamylase (OTC; EC 2.1.3.3) is a ubiquitous enzyme found in almost all organisms, including vertebrates, microorganisms, and plants. Anabolic, mostly trimeric OTCs catalyze the production of L-citrulline from L-ornithine which is a part of the urea cycle. In eukaryotes, such OTC localizes to the mitochondrial matrix, partially bound to the mitochondrial inner membrane and part of channeling multi-enzyme assemblies. In mammals, mainly two organs express OTC: the liver, where it is an integral part of the urea cycle, and the intestine, where it synthesizes citrulline for export and plays a major role in amino acid homeostasis, particularly of L-glutamine and L-arginine. Here, we give an overview on OTC genes and proteins, their tissue distribution, regulation, and physiological function, emphasizing the importance of OTC and urea cycle enzymes for metabolic regulation in human health and disease. Finally, we summarize the current knowledge of OTC deficiency, a rare X-linked human genetic disorder, and its emerging role in various chronic pathologies.

show abstract

“…The implicated interactions between the transamination and amino acid metabolism pathways in HCC cells may be involved in the development of HCC mediated by downregulated OTC. Additionally, studies have reported that OTC may influence liver regeneration though participating in certain unidentified signaling pathways, independent of its known enzyme activity (29). Further investigations are required to explain whether the effect of OTC on HCC cells relies on the protein itself or its catalytic properties and possible targets.…”

Section: Discussionmentioning

confidence: 99%

Ornithine transcarbamylase downregulation is associated with poor prognosis in hepatocellular carcinoma

Cai

Cheng

et al. 2019

Oncol Lett

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-associated mortalities worldwide. The role of ornithine transcarbamylase (OTC) in HCC remains unclear. In the present study, the expression of OTC in HCC was analyzed based on datasets from the Gene Expression Omnibus database of the National Center for Biotechnology Information and further confirmed by immunohistochemistry, western blotting analysis and reverse transcription-quantitative polymerase chain reaction assays on clinical samples and cell lines. Furthermore, the associations between OTC expression and clinicopathological parameters as well as clinical outcome, including the overall and disease-free survival rates were analyzed. Finally, the effect of OTC on HCC cells was measured using proliferation, bromodeoxyuridine and colony-formation assays. Lower OTC expression was observed in HCC cells and tissues compared with primary human hepatocytes. Further investigation demonstrated that low expression of OTC in HCC was associated with larger tumor size and advanced grade. A Kaplan-Meier analysis revealed that patients with lower levels of OTC exhibited shorter overall and disease-free survival times. Notably, OTC silencing with RNA interference facilitated cell proliferation in HCC SK-Hep-1 and Huh-7 cells. However, overexpression of OTC led to inhibition of cell proliferation. In conclusion, the present study identified a novel role of OTC in HCC development, providing a potential novel therapeutic target for this disease.

show abstract

Molecular and Biochemical Features of the Mitochondrial Enzyme Ornithine Transcarbamylase: A Possible New Role as a Signaling Factor

Cited by 12 publications

References 52 publications

Comparative hepatic proteome analysis between lean and obese rats fed a high‐fat diet reveals the existence of gender differences

Comparative hepatic proteome analysis between lean and obese rats fed a high‐fat diet reveals the existence of gender differences

Ornithine Transcarbamylase – From Structure to Metabolism: An Update

Ornithine transcarbamylase downregulation is associated with poor prognosis in hepatocellular carcinoma

Contact Info

Product

Resources

About