Theoretical studies of the quinolinic acid to nicotinic acid mononucleotide transformation

Aleksandr Rozenberg, Jeehiun K. Lee

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

(Chemical Equation Presented) 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.

Original languageEnglish (US)
Pages (from-to)9314-9319
Number of pages6
JournalJournal of Organic Chemistry
Volume73
Issue number23
DOIs
StatePublished - Dec 5 2008

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

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