Document Detail


Theoretical studies of the quinolinic acid to nicotinic acid mononucleotide transformation.
MedLine Citation:
PMID:  18954112     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Aleksandr Rozenberg; Jeehiun K Lee
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  The Journal of organic chemistry     Volume:  73     ISSN:  1520-6904     ISO Abbreviation:  J. Org. Chem.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2010-06-21     Completed Date:  2010-10-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985193R     Medline TA:  J Org Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9314-9     Citation Subset:  IM    
Affiliation:
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA.
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MeSH Terms
Descriptor/Qualifier:
Carbon / 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:
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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