Further evidence as to the nature of the transition state leading to decarboxylation of 2-pyridinecarboxylic acids. Electrical effects in the transition state

Brown, Ellis V.; Moser, Russell J.

doi:10.1021/jo00802a019

Cited by 15 publications

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“…k,, is the rate constant for decarboxylation of the isoelectric species and k, that for the anion. Then [2] and [3] define the amino acid ionization constants and [4] gives the stoichiometric concentration of amino acid [C].…”

Section: -Metlzylpicolinic Acidmentioning

confidence: 99%

Kinetics and mechanism of decarboxylation of some pyridinecarboxylic acids in aqueous solution. II

Dunn¹,

Thimm²

1977

Can. J. Chem.

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Six 3-substituted picolinic acids were synthesized and decarboxylated in buffered aqueous solutions of ionic strength 1.0 at 150 and/or 95°C. 3-Amino-and 3-hydroxypicolinic acids appear to decarboxylate by initial protonation, but the others fit the requirements of the Hammick mechanism for picolinic acid decarboxylation. Both electron-withdrawing and electron-releasing 3-substituents accelerate decarboxylation in picolinic acids but inhibit decarboxylation in their anions. Acceleration in the acids is considered to be the result of interference by 3-substituents with coplanarity of the carboxyl group and the aromatic nucleus. This reduces the order of the bond between the carboxyl group and the ring, thus facilitating bond breaking. In decarboxylation of the anions water appears to play a critical role, since picolinate ions have not been observed to decarboxylate in any other solvent, including ethylene glycol. It is proposed that water forms a hydrogen-bonded bridge between carboxylate oxygen and aromatic nitrogen, so that as the carbon-carbon bond breaks a nitrogen-hydrogen bond is formed. This may provide a lower energy path through an ylide intermediate than would be required if the picolinate ion were to decarboxylate to a 2-pyridyl carbanion. Chem. 55, 1342Chem. 55, (1977. On a synthetise six acides picoliniques substitues en position 3 et on les a dCcarboxyles dans des solutions aqueuses tamponnes de force ionique 1 .O, a 150 et/ou 95'C. I1 semble que les acides amino-3 et hydroxy-3 picoliniques se decarboxylent par une protonation initiale; toutefois les autres presentent les caracteristiques necessaires pour le mecanisme propose par Hammick pour la dCcarboxylation de I'acide picolinique. Les substituants en position 3 qui attirent les electrons ainsi que ceux qui repoussent les electrons accelerent la decarboxylation des acides picoliniques mais inhibent la decarboxylation de leurs anions. On considere que I'accelCration dans les acides provient d'une interference, par les substituants en position 3, sur la coplanarite du groupe carboxyle et du noyau aromatique. Cet effet reduit l'ordre de la liaison entre le groupement carboxyle et le cycle et facilite ainsi le bris du lien. Dans le cas de la decarboxylation des anions, il sernble que l'eau joue un r6le critique puisque l'on n'a jarnais observe la decarboxylation des ions picolinates dans d'autres solvants, m&me i'ethylene glycol. On suggere que l'eau forme des ponts hydrogene entre I'oxygkne du carboxylate et I'azote du cycle arornatique provoquant la formation d'un lien azote-hydrogene au moment oh le lien carbone-carbone se brise. Ce processus pourrait fournir une voie requtrant une energie plus basse, via un ylide intermediaire, que celle qui serait requise si l'ion picolinate se decarboxylait par I'intermidiaire d'un carbanion pyridyle-2.[Traduit par le journal]

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Section: -Metlzylpicolinic Acidmentioning

confidence: 99%

Kinetics and mechanism of decarboxylation of some pyridinecarboxylic acids in aqueous solution. II

Dunn¹,

Thimm²

1977

Can. J. Chem.

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“…Thus, it is not clear if the decarboxylation is enzymatic or spontaneous. Based on inhibition studies, the putative QAMN intermediate was proposed to decarboxylate via an ylide mechanism ,, . The ylide mechanism has also been proposed for the decarboxylation of orotidine 5′-monophosphate by OMP decarboxylase, which, like QAPRTase, is an α/β barrel enzyme and has no cofactor requirement .…”

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confidence: 99%

“…Among cofactorless decarboxylases, a lysine amino group was recently proposed to act as the initial carboxyl receptor in a bacterial oxaloacetate decarboxylase . Studies with model compounds showed that nonenzymatic decarboxylation of pyridine-2-carboxylic acids substituted with a carboxyl group at position 3 occurred spontaneously , . However, the rate of the QAPRTase reaction is 5 orders of magnitude faster than the spontaneous decarboxylation of the model compounds.…”

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confidence: 99%

Roles for Cationic Residues at the Quinolinic Acid Binding Site of Quinolinate Phosphoribosyltransferase

Bello

Grubmeyer

2010

Biochemistry

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Quinolinic acid phosphoribosyltransferase (QAPRTase, EC 2.4.2.19) forms nicotinate mononucleotide (NAMN) from quinolinic acid (QA) and 5-phosphoribosyl 1-pyrophosphate (PRPP). Previously determined crystal structures of QAPRTase•QA and QAPRTase•PA•PRPP complexes show positively charged residues (Arg118, Arg152, Arg175, Lys185 and His188) lining the QA binding site. To assess the roles of these residues in the Salmonella typhimurium QAPRTase reaction, they were individually mutated to alanine and the recombinant proteins overexpressed and purified from a recombineered E. coli strain that lacks the QAPRTase gene. Gel filtration indicated that the mutations did not affect the dimeric aggregation state of the enzymes. Arg175 is critical for the QAPRTase reaction, and its mutation to alanine produced an inactive enzyme. The k cat values for R152A and K185A were reduced by 33-fold and 625-fold, and binding affinity of PRPP and QA to the enzymes decreased. R152A and K185A mutants displayed 116-fold and 83-fold increases in activity towards the normally inactive QA analog, nicotinic acid (NA), indicating roles for these residues in defining the substrate specificity of QAPRTase. Moreover, K185A QAPRTase displayed a 300-fold higher k cat /K m for NA over the natural substrate QA. Pre-steady state analysis of K185A with QA revealed a burst of nucleotide formation followed by a slower steady-state rate, unlike the linear kinetics of WT. Intriguingly, pre-steady state analysis of K185A with NA produced a rapid but linear rate for NAMN formation. The result implies a critical role for Lys185 in the chemistry of the QAPRTase intermediate. Arg118 is an essential residue that reaches across the dimer interface. Mutation of Arg118 to alanine resulted in 5000-fold decrease in k cat value, and a decrease in the binding affinity of QA and PRPP to R152A. Equimolar mixtures of R118A with inactive or virtually inactive mutants produced approximately 50% of the enzymatic activity of WT, establishing an interfacial role for Arg118 during catalysis.Quinolinate phosphoribosyltransferase (QAPRTase, EC 2.4.2.19) is a type II phosphoribosyltransferase (PRTase) that participates in the de novo biosynthesis of the pyridine coenzyme, NAD (1,2). Recently, nicotinate phosphoribosyltransferase (NAPRTase) and nicotinamide phosphoribosyltransferase (NMPRTase), involved in the salvage pathways of NAD biosynthesis, have been classified as type II PRTases (3-5). The type II PRTases catalyze the transfer of a phosphoribosyl moiety from 5-phosphoribosyl-1-pyrophosphate (PRPP) to their specific substrates. The phosphoribosyl transfer reaction catalyzed by QAPRTase is linked to an irreversible decarboxylation reaction at position 2 of the quinolinic acid (QA) ring, with no cofactor requirement (2,6).The nadC gene of Salmonella typhimurium which encodes QAPRTase is one of the three nonessential genes involved in de novo NAD biosynthesis (7). Unlike the other two genes (nadA (L-aspartate oxidase) and nadB (quinolinate synthase)), which are known to b...

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ChemInform Abstract: WEITERE BEWEISE FUER DIE NATUR DES UEBERGANGSZUSTANDES BEI DER DECARBOXYLIERUNG VON 2‐PYRIDIN‐CARBONSAEUREN, ELEKTRISCHE EINFLUESSE BEIM UEBERGANGSZUSTAND

Brown¹,

Moser²

1971

Chemischer Informationsdienst. Organische Chemie

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Further evidence as to the nature of the transition state leading to decarboxylation of 2-pyridinecarboxylic acids. Electrical effects in the transition state

Cited by 15 publications

References 0 publications

Kinetics and mechanism of decarboxylation of some pyridinecarboxylic acids in aqueous solution. II

Kinetics and mechanism of decarboxylation of some pyridinecarboxylic acids in aqueous solution. II

Roles for Cationic Residues at the Quinolinic Acid Binding Site of Quinolinate Phosphoribosyltransferase

ChemInform Abstract: WEITERE BEWEISE FUER DIE NATUR DES UEBERGANGSZUSTANDES BEI DER DECARBOXYLIERUNG VON 2‐PYRIDIN‐CARBONSAEUREN, ELEKTRISCHE EINFLUESSE BEIM UEBERGANGSZUSTAND

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