A MOLECULAR MECHANISM FOR ENZYMATIC DEHYDROGENATIONS INVOLVING PYRIDINE NUCLEOTIDES

1960 ◽  
Vol 38 (10) ◽  
pp. 1185-1194 ◽  
Author(s):  
Richard M. Krupka ◽  
Keith J. Laidler
Keyword(s):  
Hydrogen Bonding ◽  
Hydrogen Transfer ◽  
Nucleophilic Attack ◽  
Pyridine Nucleotides ◽  
Basic Group ◽  
Rate Determining Step ◽  
Enzyme Substrate ◽  
Group B ◽  
Hydroxyl Hydrogen Atom ◽  
Hydroxyl Hydrogen

The main kinetic results obtained with the dehydrogenases are briefly summarized. It is shown that the mechanism must involve a ternary enzyme–substrate–coenzyme complex, that acidic and basic groups on the enzyme surface must be involved in the reaction, and that there appears to be a transfer of the substrate from one site to another in the rate-determining step. It is suggested that this step is the actual hydrogen-transfer process. When the substrate is undergoing oxidation, this transfer is brought about by a nucleophilic attack by a basic group B−at the enzyme's active center. This attack may be on a hydroxyl hydrogen atom, and is considered to lead to the transfer of H−from the substrate to the coenzyme. The product is held to the enzyme by hydrogen bonding between the group BH (formed by the addition of a proton to the basic group B−) and the carbonyl group on the substrate.

A MOLECULAR MECHANISM FOR ENZYMATIC DEHYDROGENATIONS INVOLVING PYRIDINE NUCLEOTIDES

1960 ◽  
Vol 38 (1) ◽  
pp. 1185-1194 ◽  
Author(s):  
Richard M. Krupka ◽  
Keith J. Laidler
Keyword(s):  
Hydrogen Bonding ◽  
Hydrogen Transfer ◽  
Nucleophilic Attack ◽  
Pyridine Nucleotides ◽  
Basic Group ◽  
Rate Determining Step ◽  
Enzyme Substrate ◽  
Group B ◽  
Hydroxyl Hydrogen Atom ◽  
Hydroxyl Hydrogen

The main kinetic results obtained with the dehydrogenases are briefly summarized. It is shown that the mechanism must involve a ternary enzyme–substrate–coenzyme complex, that acidic and basic groups on the enzyme surface must be involved in the reaction, and that there appears to be a transfer of the substrate from one site to another in the rate-determining step. It is suggested that this step is the actual hydrogen-transfer process. When the substrate is undergoing oxidation, this transfer is brought about by a nucleophilic attack by a basic group B−at the enzyme's active center. This attack may be on a hydroxyl hydrogen atom, and is considered to lead to the transfer of H−from the substrate to the coenzyme. The product is held to the enzyme by hydrogen bonding between the group BH (formed by the addition of a proton to the basic group B−) and the carbonyl group on the substrate.

scholarly journals Understanding the reaction mechanism of the regioselective piperidinolysis of aryl 1-(2,4-dinitronaphthyl) ethers in DMSO: Kinetic and DFT studies

2021 ◽  
Vol 46 ◽  
pp. 146867832110274
Author(s):  
Yasmen M Moghazy ◽  
Nagwa MM Hamada ◽  
Magda F Fathalla ◽  
Yasser R Elmarassi ◽  
Ezzat A Hamed ◽  
...  
Keyword(s):  
Carbon Atom ◽  
Density Functional ◽  
Function Analysis ◽  
Density Functional Theory Method ◽  
Activation Parameters ◽  
Kinetic Studies ◽  
Nucleophilic Attack ◽  
Common Mechanism ◽  
Slow Step ◽  
Rate Determining Step

Reactions of aryl 1-(2,4-dinitronaphthyl) ethers with piperidine in dimethyl sulfoxide at 25oC resulted in substitution of the aryloxy group at the ipso carbon atom. The reaction was measured spectrophotochemically and the kinetic studies suggested that the titled reaction is accurately third order. The mechanism is began by fast nucleophilic attack of piperidine on C1 to form zwitterion intermediate (I) followed by deprotonation of zwitterion intermediate (I) to the Meisenheimer ion (II) in a slow step, that is, SB catalysis. The regular variation of activation parameters suggested that the reaction proceeded through a common mechanism. The Hammett equation using reaction constant σo values and Brønsted coefficient value showed that the reaction is poorly dependent on aryloxy substituent and the reaction was significantly associative and Meisenheimer intermediate-like. The mechanism of piperidinolysis has been theoretically investigated using density functional theory method using B3LYP/6-311G(d,p) computational level. The combination between experimental and computational studies predicts what mechanism is followed either through uncatalyzed or catalyzed reaction pathways, that is, SB and SB-GA. The global parameters of the reactants, the proposed activated complexes, and the local Fukui function analysis explained that C1 carbon atom is the most electrophilic center of ether. Also, kinetics and theoretical calculation of activation energies indicated that the mechanism of the piperidinolysis passed through a two-step mechanism and the proton transfer process was the rate determining step.

The influence of pH and inhibitors on the kinetics of enzyme reactions involving two intermediates

1967 ◽  
Vol 45 (5) ◽  
pp. 539-546 ◽  
Author(s):  
Harvey Kaplan ◽  
Keith J. Laidler
Keyword(s):  
Steady State ◽  
Ph Dependence ◽  
Free Enzyme ◽  
State Equations ◽  
Enzyme Reactions ◽  
Substrate Complex ◽  
Rate Determining Step ◽  
Enzyme Substrate ◽  
Special Cases ◽  
Influence Of Ph

General steady-state equations are worked out for enzyme reactions which occur according to the scheme [Formula: see text]Equations showing the pH dependence of the kinetic parameters are developed in a form which distinguishes between essential and nonessential ionizing groups. The pK dependence of [Formula: see text], the second-order constant extrapolated to zero substrate constant, gives pK values for groups which ionize on the free enzyme, but reveals such a pK only if the corresponding group is also involved in the breakdown of the Michaelis complex. General steady-state equations are also developed for the case in which an inhibitor can combine with the free enzyme, the enzyme–substrate complex, and also a second intermediate (e.g. an acyl enzyme). The equations are given in a form that is convenient for analyzing the experimental results, and a number of special cases are considered. It is shown how the type of inhibition depends not only on the nature of the inhibitor but also on that of the substrate, an important factor being the rate-determining step of the reaction. Examples of the various kinds of behavior are given.

Metal complex catalyzed reactions of anils. III. Kinetic and mechanistic studies

1977 ◽  
Vol 55 (12) ◽  
pp. 2432-2441 ◽  
Author(s):  
A. R. Boate ◽  
D. R. Eaton
Keyword(s):  
Aqueous Solution ◽  
Metal Complex ◽  
Metal Atom ◽  
Nucleophilic Attack ◽  
Mechanistic Studies ◽  
Acetone Molecule ◽  
Rate Determining Step ◽  
Catalyzed Reactions ◽  
Kinetics Of ◽  
Hydrolysis Of

The kinetics of the homogeneously catalyzed formation and hydrolysis of anils in non-aqueous solution have been studied. The catalysts used are zinc complexes of thiourea. It is shown that all the evidence obtained, kinetic and otherwise, is consistent with a model in which the rate determining step for anil formation is nucleophilic attack by an aniline held in the second coordination sphere of the metal complex on an acetone molecule directly bound to the metal atom. Analogous mechanisms are suggested for anil hydrolysis and for transimination.

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