Mechanism of carbinolamine formation

Sayer, Jane M.; Pinsky, Benjamin M.; Schönbrunn, Agnes; Washtien, Wendy L.

doi:10.1021/ja00833a027

Cited by 113 publications

(99 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…7, also makes a hydrogen bond to the C 2 hydroxyl in the MBP structure and Substrate Cleavage-A multiple catalytic role for Glu-187 in FBP aldolase catalysis was advanced from enzymological data that implicated the residue in C 3 -C 4 bond cleavage as well as in proton transfers at the level of the ketimine intermediate (11). The structural analysis herein reveals Glu-187 participation in hydrogen bond formation with key reaction intermediates (7,45). A catalytic mechanism by which to promote cleavage of the C-C bond in class I FBP aldolases integrating enzymology and structure data is outlined in Scheme II.…”

Section: (ϳ08 å Inmentioning

confidence: 92%

High Resolution Reaction Intermediates of Rabbit Muscle Fructose-1,6-bisphosphate Aldolase

St-Jean

Lafrance‐Vanasse

Liotard

et al. 2005

Journal of Biological Chemistry

105

View full text Add to dashboard Cite

Crystal structures were determined to 1.8 Å resolution of the glycolytic enzyme fructose-1,6-bis(phosphate) aldolase trapped in complex with its substrate and a competitive inhibitor, mannitol-1,6-bis(phosphate). The enzyme substrate complex corresponded to the postulated Schiff base intermediate and has reaction geometry consistent with incipient C 3 -C 4 bond cleavage catalyzed by Glu-187, which is adjacent to the Schiff base forming Lys-229. Atom arrangement about the cleaved bond in the reaction intermediate mimics a pericyclic transition state occurring in nonenzymatic aldol condensations. Lys-146 hydrogen-bonds the substrate C 4 hydroxyl and assists substrate cleavage by stabilizing the developing negative charge on the C 4 hydroxyl during proton abstraction. Mannitol-1,6-bis(phosphate) forms a noncovalent complex in the active site whose binding geometry mimics the covalent carbinolamine precursor. Glu-187 hydrogen-bonds the C 2 hydroxyl of the inhibitor in the enzyme complex, substantiating a proton transfer role by Glu-187 in catalyzing the conversion of the carbinolamine intermediate to Schiff base. Modeling of the acyclic substrate configuration into the active site shows Glu-187, in acid form, hydrogen-bonding both substrate C 2 carbonyl and C 4 hydroxyl, thereby aligning the substrate ketose for nucleophilic attack by Lys-229. The multifunctional role of Glu-187 epitomizes a canonical mechanistic feature conserved in Schiff base-forming aldolases catalyzing carbohydrate metabolism. Trapping of tagatose-1,6-bis(phosphate), a diastereoisomer of fructose 1,6-bis(phosphate), displayed stereospecific discrimination and reduced ketohexose binding specificity. Each ligand induces homologous conformational changes in two adjacent ␣-helical regions that promote phosphate binding in the active site.Aldolases are ubiquitous enzymes and have been a subject of continuous interest because of their ability to catalyze carboncarbon bond formation in living organisms. Their role is best known in glycolysis, where fructose 1,6-bis(phosphate) (FBP) 1 aldolases (EC 4.1.2.13) promote the reversible cleavage of FBP to triose phosphates, D-glyceraldehyde 3-phosphate and dihydroxyacetone phosphate (DHAP). The class I enzyme uses covalent catalysis, implicating a Schiff base formed between a lysine residue on the enzyme and a ketose substrate. In vertebrates, there are three tissue-specific class I aldolases (aldolase A (found in skeletal muscle and red blood cells), aldolase B (found in liver, kidney, and small intestine), and aldolase C (found in neuronal tissues and smooth muscle)), and they are distinguishable on the basis of immunological and kinetic properties (1). The catalytic mechanism has been extensively studied using class I aldolase A from rabbit muscle, and key intermediates are depicted in Scheme I.In the forward reaction, a reactive lysine residue in the active site attacks the ketose (2) of the acyclic FBP substrate (3, 4). Transient formation of a dipolar tetrahedral carbinolamine with the keto function yi...

show abstract

Section: (ϳ08 å Inmentioning

confidence: 92%

High Resolution Reaction Intermediates of Rabbit Muscle Fructose-1,6-bisphosphate Aldolase

St-Jean

Lafrance‐Vanasse

Liotard

et al. 2005

Journal of Biological Chemistry

105

View full text Add to dashboard Cite

show abstract

“…Thus, experimental procedures for the preparation of aliphatic aldimines have become more specific in order to improve the yield 19 . The reaction mechanism of amine addition to carbonyl compounds in aqueous solution has been studied at the experimental level [20][21][22][23][24] , and some theoretical studies have been reported 25,26 . Sayer et al has proposed a general mechanism for this reaction in aqueous solution and at variable pH.…”

Section: Introductionmentioning

confidence: 99%

Theoretical and experimental investigation of the formation of E- and Z-Aldimines from the reaction of methylamine with acetaldehyde

Pliego¹,

Alcântara²,

Veloso³

et al. 1999

J. Braz. Chem. Soc.

View full text Add to dashboard Cite

A reação entre metilamina e acetaldeído em pentano a 230 K leva à formação das aldiminas Ee Z-, sendo o isômero Z-o produto principal e gerado sob controle cinético. O isômero E-é mais estável do que o Z-por 3.3 kcal/mol (∆G*). Os cálculos ab initio mostraram que a etapa bimolecular de adição ocorre por um processo concertado, com formação da ligação C-N e transferência de próton através de um estado de transição de quatro centros. O intermediário zwiteriônico, frequentemente invocado neste tipo de reação, não existe como um mínimo na superfície de energia potencial. Entretanto, a energia livre de ativação para o mecanismo concertado é muito alta, e não é capaz de explicar a cinética deste processo. O mesmo acorre com a etapa de eliminação de água para formar a imina, ou seja, possui uma barreira de ativação muito alta. Estes resultados implicam que tanto a etapa de adição, como a de eliminação, devem ocorrer por um mecanismo de catálise.O isômero Z-pode se interconverter para a forma E-através de uma inversão sobre o nitrogênio sp 2 . A 298.15 K, a energia livre de ativação para este processo foi calculada como sendo 27.0 kcal/mol, o que leva a um tempo de vida de quatro meses para este isômero.The reaction of methylamine with acetaldehyde in pentane at 230 K leads to formation of both E-and Z-aldimines, the Z-isomer being the main product and generated upon kinetic control. The E-form is more stable than the Z-form by 3.3 kcal/mol (∆G*). Ab initio calculations have indicated that a tetrahedral zwitterion intermediate is not formed, and the bimolecular process, forming the aminoalcohol intermediate, occurs through a four center transition state, with concerted formation of C-N bond and proton transfer. However, the predicted ∆G* ≠ is very high, indicating that the true mechanism for this step is not bimolecular. A catalyzed pathway must be actuating. The following step, unimolecular elimination of water, also presents a very high activation free energy. Similarly, a catalyzed mechanism is needed. The isomerization from the Z-form to the E-form through inversion of the nitrogen atom has a predicted ∆G* ≠ of 27.0 kcal/mol at 298.15 K, resulting in a lifetime of four months for the Z-isomer.

show abstract

“…It is well known that the primary and secondary amines react by nucleophilic addition with carbonyl compounds to give intermediate tetrahedral addition products called hemiaminals [14] as a first step of condensation reaction [15]. The next step is the dehydration of that compound which leads to the formation of stable imines, enamines, hydrazones and related compounds [16].…”

Section: Open Accessmentioning

confidence: 99%

A Study on the Condensation Reaction of 4-Amino-3,5-dimethyl-1,2,4-triazole with Benzaldehydes: Structure and Spectroscopic Properties of Some New Stable Hemiaminals

Wajda-Hermanowicz¹,

Pieniążczak²,

Zatajska³

et al. 2015

Molecules

View full text Add to dashboard Cite

Studies on the stable hemiaminals and Schiff bases formation in the reaction of substituted benzaldehydes with primary 3,5-dimethyl-1,2,4-triazole 4-amine were carried out under neutral conditions. These products were investigated by IR, Raman, MS, 1 H-and 13 C-NMR spectra as well as by X-ray crystallography. The effect of reaction conditions: temperature, polarity of the solvents utilized, substrate concentration and the ortho and para benzaldehyde substituents on the yield of products was also examined.

show abstract

Mechanism of carbinolamine formation

Cited by 113 publications

References 6 publications

High Resolution Reaction Intermediates of Rabbit Muscle Fructose-1,6-bisphosphate Aldolase

High Resolution Reaction Intermediates of Rabbit Muscle Fructose-1,6-bisphosphate Aldolase

Theoretical and experimental investigation of the formation of E- and Z-Aldimines from the reaction of methylamine with acetaldehyde

A Study on the Condensation Reaction of 4-Amino-3,5-dimethyl-1,2,4-triazole with Benzaldehydes: Structure and Spectroscopic Properties of Some New Stable Hemiaminals

Contact Info

Product

Resources

About