FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2078633192> ?p ?o ?g. }

• W2078633192 endingPage "241" @default.
• W2078633192 startingPage "237" @default.
• W2078633192 abstract "Here, the authors identify a previously unknown regulatory strategy used by Escherichia coli to control end-product levels of the pyrimidine biosynthetic pathway: this involves feedback regulation of the near-terminal pathway enzyme UMP kinase, with accumulation of UMP prevented by its degradation to uridine through UmpH, a phosphatase with a previously unknown function. The control of the concentrations and fluxes of the thousand or so metabolites in a living cell such as Escherichia coli occurs via regulation of enzyme concentrations, activities and substrate occupancies. De novo pyrimidine biosynthesis has been reported to be regulated at the first committed pathway step (catalysed by aspartate transcarbamoylase) and at the previous (carbamoyl phosphate synthetase) step. Here the authors identify a novel regulatory strategy — an overflow pathway from UMP to uracil — that E. coli cells use to avoid the accumulation of an excess of the end products of pyrimidine biosynthesis. The process is analogous to that seen in central carbon metabolism, where excessive sugar catabolism leads to buildup of pyruvate that can be excreted as lactate, ethanol or acetate. Cellular metabolism converts available nutrients into usable energy and biomass precursors. The process is regulated to facilitate efficient nutrient use and metabolic homeostasis. Feedback inhibition of the first committed step of a pathway by its final product is a classical means of controlling biosynthesis1,2,3,4. In a canonical example, the first committed enzyme in the pyrimidine pathway in Escherichia coli is allosterically inhibited by cytidine triphosphate1,4,5. The physiological consequences of disrupting this regulation, however, have not been previously explored. Here we identify an alternative regulatory strategy that enables precise control of pyrimidine pathway end-product levels, even in the presence of dysregulated biosynthetic flux. The mechanism involves cooperative feedback regulation of the near-terminal pathway enzyme uridine monophosphate kinase6. Such feedback leads to build-up of the pathway intermediate uridine monophosphate, which is in turn degraded by a conserved phosphatase, here termed UmpH, with previously unknown physiological function7,8. Such directed overflow metabolism allows homeostasis of uridine triphosphate and cytidine triphosphate levels at the expense of uracil excretion and slower growth during energy limitation. Disruption of the directed overflow regulatory mechanism impairs growth in pyrimidine-rich environments. Thus, pyrimidine homeostasis involves dual regulatory strategies, with classical feedback inhibition enhancing metabolic efficiency and directed overflow metabolism ensuring end-product homeostasis." @default.
• W2078633192 created "2016-06-24" @default.
• W2078633192 creator A5002097234 @default.
• W2078633192 creator A5016314947 @default.
• W2078633192 creator A5053467552 @default.
• W2078633192 creator A5060954396 @default.
• W2078633192 creator A5086885566 @default.
• W2078633192 date "2013-07-31" @default.
• W2078633192 modified "2023-10-17" @default.
• W2078633192 title "Pyrimidine homeostasis is accomplished by directed overflow metabolism" @default.
• W2078633192 cites W1545921898 @default.
• W2078633192 cites W1568502048 @default.
• W2078633192 cites W1642162696 @default.
• W2078633192 cites W1781531090 @default.
• W2078633192 cites W1965920457 @default.
• W2078633192 cites W1967946076 @default.
• W2078633192 cites W1977473423 @default.
• W2078633192 cites W1994124478 @default.
• W2078633192 cites W2001137003 @default.
• W2078633192 cites W2001958358 @default.
• W2078633192 cites W2004235182 @default.
• W2078633192 cites W2006970791 @default.
• W2078633192 cites W2007013450 @default.
• W2078633192 cites W2017608263 @default.
• W2078633192 cites W2026583779 @default.
• W2078633192 cites W2037911829 @default.
• W2078633192 cites W2038251804 @default.
• W2078633192 cites W2083996487 @default.
• W2078633192 cites W2090656601 @default.
• W2078633192 cites W2091149031 @default.
• W2078633192 cites W2092504964 @default.
• W2078633192 cites W2097758310 @default.
• W2078633192 cites W2102489535 @default.
• W2078633192 cites W2111481396 @default.
• W2078633192 cites W2111967267 @default.
• W2078633192 cites W2116137883 @default.
• W2078633192 cites W2116976883 @default.
• W2078633192 cites W2124737787 @default.
• W2078633192 cites W2125630053 @default.
• W2078633192 cites W2139786345 @default.
• W2078633192 cites W2139915240 @default.
• W2078633192 cites W2143335101 @default.
• W2078633192 cites W2144455805 @default.
• W2078633192 cites W2147189708 @default.
• W2078633192 cites W2150473143 @default.
• W2078633192 cites W2162377372 @default.
• W2078633192 cites W2167157054 @default.
• W2078633192 cites W2339493109 @default.
• W2078633192 cites W2345278067 @default.
• W2078633192 cites W3085746353 @default.
• W2078633192 doi "https://doi.org/10.1038/nature12445" @default.
• W2078633192 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4470420" @default.
• W2078633192 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23903661" @default.
• W2078633192 hasPublicationYear "2013" @default.
• W2078633192 type Work @default.
• W2078633192 sameAs 2078633192 @default.
• W2078633192 citedByCount "87" @default.
• W2078633192 countsByYear W20786331922013 @default.
• W2078633192 countsByYear W20786331922014 @default.
• W2078633192 countsByYear W20786331922015 @default.
• W2078633192 countsByYear W20786331922016 @default.
• W2078633192 countsByYear W20786331922017 @default.
• W2078633192 countsByYear W20786331922018 @default.
• W2078633192 countsByYear W20786331922019 @default.
• W2078633192 countsByYear W20786331922020 @default.
• W2078633192 countsByYear W20786331922021 @default.
• W2078633192 countsByYear W20786331922022 @default.
• W2078633192 countsByYear W20786331922023 @default.
• W2078633192 crossrefType "journal-article" @default.
• W2078633192 hasAuthorship W2078633192A5002097234 @default.
• W2078633192 hasAuthorship W2078633192A5016314947 @default.
• W2078633192 hasAuthorship W2078633192A5053467552 @default.
• W2078633192 hasAuthorship W2078633192A5060954396 @default.
• W2078633192 hasAuthorship W2078633192A5086885566 @default.
• W2078633192 hasBestOaLocation W20786331922 @default.
• W2078633192 hasConcept C104317684 @default.
• W2078633192 hasConcept C181199279 @default.
• W2078633192 hasConcept C185592680 @default.
• W2078633192 hasConcept C192989942 @default.
• W2078633192 hasConcept C197248121 @default.
• W2078633192 hasConcept C200159599 @default.
• W2078633192 hasConcept C2776476023 @default.
• W2078633192 hasConcept C2779321679 @default.
• W2078633192 hasConcept C2779554091 @default.
• W2078633192 hasConcept C2781184954 @default.
• W2078633192 hasConcept C547475151 @default.
• W2078633192 hasConcept C552990157 @default.
• W2078633192 hasConcept C55493867 @default.
• W2078633192 hasConcept C62231903 @default.
• W2078633192 hasConcept C86803240 @default.
• W2078633192 hasConcept C96942376 @default.
• W2078633192 hasConceptScore W2078633192C104317684 @default.
• W2078633192 hasConceptScore W2078633192C181199279 @default.
• W2078633192 hasConceptScore W2078633192C185592680 @default.
• W2078633192 hasConceptScore W2078633192C192989942 @default.
• W2078633192 hasConceptScore W2078633192C197248121 @default.
• W2078633192 hasConceptScore W2078633192C200159599 @default.
• W2078633192 hasConceptScore W2078633192C2776476023 @default.

• next