ArticleProceedings of the National Academy of Sciences of the United States of America2008
Mechanism of thermal decomposition of carbamoyl phosphate and its stabilization by aspartate and ornithine transcarbamoylases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 30 citations in OpenAlex.
- Rational engineering of facultative anaerobiosis enables commensal survival in the oxygenated gut.bioRxiv : the preprint server for biology · 2026Article
- Metabolic profiling reveals channeled de novo pyrimidine and purine biosynthesis fueled by mitochondrially generated aspartic acid in cancer cells.Nature communications · 2025Article
- Building the uracil skeleton in primitive ponds at the origins of life: carbamoylation of aspartic acid.Scientific reports · 2022Article
- Carbamoyl phosphate and its substitutes for the uracil synthesis in origins of life scenarios.Scientific reports · 2021Article
- Enhanced production of L-arginine by improving carbamoyl phosphate supply in metabolically engineered Corynebacterium crenatum.Applied microbiology and biotechnology · 2021Article
- Structure of a reaction intermediate mimic in t6A biosynthesis bound in the active site of the TsaBD heterodimer from Escherichia coli.Nucleic acids research · 2021Article
- A fragment-based approach to assess the ligandability of ArgB, ArgC, ArgD and ArgF in the L-arginine biosynthetic pathway ofComputational and structural biotechnology journal · 2021Article
- (2Cancers · 2020Article
- Author Correction: CPS1 maintains pyrimidine pools and DNA synthesis in KRAS/LKB1-mutant lung cancer cells.Nature · 2019Article
- Regulation of carbamoylphosphate synthesis in Escherichia coli: an amazing metabolite at the crossroad of arginine and pyrimidine biosynthesis.Amino acids · 2018Review
- Sources and Fates of Carbamyl Phosphate: A Labile Energy-Rich Molecule with Multiple Facets.Biology · 2018Review
- Eight Kinetically Stable but Thermodynamically Activated Molecules that Power Cell Metabolism.Chemical reviews · 2018Review
- Hyperthermophilic Carbamate Kinase Stability and AnabolicApplied and environmental microbiology · 2018Article
- Genomic and experimental evidence for multiple metabolic functions in the RidA/YjgF/YER057c/UK114 (Rid) protein family.BMC genomics · 2015Article
- Structure of the catalytic chain of Methanococcus jannaschii aspartate transcarbamoylase in a hexagonal crystal form: insights into the path of carbamoyl phosphate to the active site of the enzyme.Acta crystallographica. Section F, Structural biology and crystallization communications · 2012Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
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Abstract
Carbamoyl phosphate (CP) has a half-life for thermal decomposition of <2 s at 100 degrees C, yet this critical metabolic intermediate is found even in organisms that grow at 95-100 degrees C. We show here that the binding of CP to the enzymes aspartate and ornithine transcarbamoylase reduces the rate of thermal decomposition of CP by a factor of >5,000. Both of these transcarbamoylases use an ordered-binding mechanism in which CP binds first, allowing the formation of an enzyme.CP complex. To understand how the enzyme.CP complex is able to stabilize CP we investigated the mechanism of the thermal decomposition of CP in aqueous solution in the absence and presence of enzyme. By quantum mechanics/molecular mechanics calculations we show that the critical step in the thermal decomposition of CP in aqueous solution, in the absence of enzyme, involves the breaking of the C O bond facilitated by intramolecular proton transfer from the amine to the phosphate. Furthermore, we demonstrate that the binding of CP to the active sites of these enzymes significantly inhibits this process by restricting the accessible conformations of the bound ligand to those disfavoring the reactive geometry. These results not only provide insight into the reaction pathways for the thermal decomposition of free CP in an aqueous solution but also show why these reaction pathways are not accessible when the metabolite is bound to the active sites of these transcarbamoylases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.