Carbamoyl phosphate and its substitutes for the uracil synthesis in origins of life scenarios

Abstract The first step of pyrimidine synthesis along the orotate pathway is studied to test the hypothesis of geochemical continuity of protometabolic pathways at the origins of life. Carbamoyl phosphate (CP) is the first high-energy building block that intervenes in the in vivo synthesis of the ur...

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Autores principales:	Louis M. P. Ter-Ovanessian, Baptiste Rigaud, Alberto Mezzetti, Jean-François Lambert, Marie-Christine Maurel
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/b15ae8f9ad70435382ae8a9240e4c989
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spelling	oai:doaj.org-article:b15ae8f9ad70435382ae8a9240e4c9892021-12-02T17:37:29ZCarbamoyl phosphate and its substitutes for the uracil synthesis in origins of life scenarios10.1038/s41598-021-98747-62045-2322https://doaj.org/article/b15ae8f9ad70435382ae8a9240e4c9892021-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-98747-6https://doaj.org/toc/2045-2322Abstract The first step of pyrimidine synthesis along the orotate pathway is studied to test the hypothesis of geochemical continuity of protometabolic pathways at the origins of life. Carbamoyl phosphate (CP) is the first high-energy building block that intervenes in the in vivo synthesis of the uracil ring of UMP. Thus, the likelihood of its occurrence in prebiotic conditions is investigated herein. The evolution of carbamoyl phosphate in water and in ammonia aqueous solutions without enzymes was characterised using ATR-IR, 31P and 13C spectroscopies. Carbamoyl phosphate initially appears stable in water at ambient conditions before transforming to cyanate and carbamate/hydrogenocarbonate species within a matter of hours. Cyanate, less labile than CP, remains a potential carbamoylating agent. In the presence of ammonia, CP decomposition occurs more rapidly and generates urea. We conclude that CP is not a likely prebiotic reagent by itself. Alternatively, cyanate and urea may be more promising substitutes for CP, because they are both “energy-rich” (high free enthalpy molecules in aqueous solutions) and kinetically inert regarding hydrolysis. Energy-rich inorganic molecules such as trimetaphosphate or phosphoramidates were also explored for their suitability as sources of carbamoyl phosphate. Although these species did not generate CP or other carbamoylating agents, they exhibited energy transduction, specifically the formation of high-energy P–N bonds. Future efforts should aim to evaluate the role of carbamoylating agents in aspartate carbamoylation, which is the following reaction in the orotate pathway.Louis M. P. Ter-OvanessianBaptiste RigaudAlberto MezzettiJean-François LambertMarie-Christine MaurelNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Louis M. P. Ter-Ovanessian Baptiste Rigaud Alberto Mezzetti Jean-François Lambert Marie-Christine Maurel Carbamoyl phosphate and its substitutes for the uracil synthesis in origins of life scenarios
description	Abstract The first step of pyrimidine synthesis along the orotate pathway is studied to test the hypothesis of geochemical continuity of protometabolic pathways at the origins of life. Carbamoyl phosphate (CP) is the first high-energy building block that intervenes in the in vivo synthesis of the uracil ring of UMP. Thus, the likelihood of its occurrence in prebiotic conditions is investigated herein. The evolution of carbamoyl phosphate in water and in ammonia aqueous solutions without enzymes was characterised using ATR-IR, 31P and 13C spectroscopies. Carbamoyl phosphate initially appears stable in water at ambient conditions before transforming to cyanate and carbamate/hydrogenocarbonate species within a matter of hours. Cyanate, less labile than CP, remains a potential carbamoylating agent. In the presence of ammonia, CP decomposition occurs more rapidly and generates urea. We conclude that CP is not a likely prebiotic reagent by itself. Alternatively, cyanate and urea may be more promising substitutes for CP, because they are both “energy-rich” (high free enthalpy molecules in aqueous solutions) and kinetically inert regarding hydrolysis. Energy-rich inorganic molecules such as trimetaphosphate or phosphoramidates were also explored for their suitability as sources of carbamoyl phosphate. Although these species did not generate CP or other carbamoylating agents, they exhibited energy transduction, specifically the formation of high-energy P–N bonds. Future efforts should aim to evaluate the role of carbamoylating agents in aspartate carbamoylation, which is the following reaction in the orotate pathway.
format	article
author	Louis M. P. Ter-Ovanessian Baptiste Rigaud Alberto Mezzetti Jean-François Lambert Marie-Christine Maurel
author_facet	Louis M. P. Ter-Ovanessian Baptiste Rigaud Alberto Mezzetti Jean-François Lambert Marie-Christine Maurel
author_sort	Louis M. P. Ter-Ovanessian
title	Carbamoyl phosphate and its substitutes for the uracil synthesis in origins of life scenarios
title_short	Carbamoyl phosphate and its substitutes for the uracil synthesis in origins of life scenarios
title_full	Carbamoyl phosphate and its substitutes for the uracil synthesis in origins of life scenarios
title_fullStr	Carbamoyl phosphate and its substitutes for the uracil synthesis in origins of life scenarios
title_full_unstemmed	Carbamoyl phosphate and its substitutes for the uracil synthesis in origins of life scenarios
title_sort	carbamoyl phosphate and its substitutes for the uracil synthesis in origins of life scenarios
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/b15ae8f9ad70435382ae8a9240e4c989
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Carbamoyl phosphate and its substitutes for the uracil synthesis in origins of life scenarios

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