| Theoretical studies of the quinolinic acid to nicotinic acid mononucleotide transformation. | |
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MedLine Citation:
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PMID: 18954112 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Quinolinate phosphoribosyl transferase (QPRTase) is an essential enzyme that catalyzes the transformation of quinolinic acid (QA) to nicotinic acid mononucleotide (NAMN), a key step on the de novo pathway for nicotinamide adenine dinucleotide (NAD) biosynthesis. We describe herein a theoretical study of the intrinsic energetics associated with the possible mechanistic pathways by which QA forms NAMN. Our main interest is in probing the decarboxylation step, which is intriguing since the product is a vinylic anion, not unlike the reaction catalyzed by orotidine 5'-monophosphate (OMP) decarboxylase, an enzyme whose mechanism is under fierce debate. Our calculations indicate that a path involving a quinolinic acid mononucleotide (QAMN) intermediate is the most energetically attractive, favoring decarboxylation. We also find that the monocarboxylate form of QAMN will decarboxylate much more favorably energetically than will the dicarboxylate form of QAMN. Furthermore, our calculations indicate that decarboxylation is not a likely first step; the substrate in such a mechanism would prefer to decarboxylate at the C3 position, not the desired C2 position. We also discuss our results in the context of existing experimental data. |
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Authors:
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Aleksandr Rozenberg; Jeehiun K Lee |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: The Journal of organic chemistry Volume: 73 ISSN: 1520-6904 ISO Abbreviation: J. Org. Chem. Publication Date: 2008 Dec |
Date Detail:
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Created Date: 2010-06-21 Completed Date: 2010-10-01 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985193R Medline TA: J Org Chem Country: United States |
Other Details:
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Languages: eng Pagination: 9314-9 Citation Subset: IM |
Affiliation:
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Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Carbon
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chemistry Carbon Dioxide / chemistry Chemistry, Organic / methods* Computational Biology / methods Decarboxylation Models, Chemical Models, Theoretical NAD / chemistry Nicotinamide Mononucleotide / analogs & derivatives*, chemistry Orotidine-5'-Phosphate Decarboxylase / chemistry Quinolinic Acid / chemistry* Software Solvents / chemistry Thermodynamics |
| Chemical | |
Reg. No./Substance:
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0/Solvents; 1094-61-7/Nicotinamide Mononucleotide; 124-38-9/Carbon Dioxide; 321-02-8/nicotinate mononucleotide; 53-84-9/NAD; 7440-44-0/Carbon; 89-00-9/Quinolinic Acid; EC 4.1.1.23/Orotidine-5'-Phosphate Decarboxylase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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