Transient Species in the Stepwise Interconversion of NADH and NAD⁺

Abstract

Two mechanisms of the interconversion of NADH and NAD+ in the coenzyme itself and in its analogues are discussed: a one-step hydride transfer and a stepwise electron-proton-electron transfer. Direct characterization of the transient species in the stepwise process and inversion of the stability order of the keto and enol tautomers is presented. The nonenzymatic and enzyme-mediated reactions of selected pyridinium salts that affect the NADH <==>NAD+ equilibrium are discussed in terms of their potential cytotoxicity.

Mechanistic Aspects of Alloxan Diabetogenic Activity: A Key Role of Keto−Enol Inversion of Dialuric Acid on Ionization

“…28,29 We have recently attempted to apply a concept of radical cation tautomerization also to nicotinamide derivatives and we concluded that, in the SCHEME 1 case of NADH derivatives, where the keto-enol tautomerization involves a 1,4-hydrogen atom shift, this process is associated with a relatively high activation barrier, but still it could proceed effectively in radical cations, which can assume a favorable geometry. 41,42 Increase of the matrix temperature significantly accelerated such processes.…”

“…The primary reaction, characteristic to the radical cations in either keto or enol form, would be their deprotonation because these species are usually characterized by very low pK a values. 42,43 All the more the primary product of such deprotonation, the semiquinone radical intermediate (AH • ), was previously characterized by HoueeLevin et al as a quite stable transient species. 23,24 In fact, the AH • radical was the only product observed upon oxidation of dialuric acid in aqueous solution under neutral or slightly acidic conditions.…”

Pulse radiolysis and steady-state analyses of the reaction between hydroethidine and superoxide and other oxidants

“…Br 2 ·-is a strong one-electron oxidant that reacts with most organic compounds via an electron-transfer mechanism. Several reports indicate that Br 2 ·-reacts rapidly with different dihydropyridines, including NADH and the primary oxidation products formed during these reactions have been previously characterized [19,20]. Thus, we decided to investigate the one-electron oxidation product formed from the reaction between HE and Br 2 ·- (Fig.…”

Synthesis of Nicotinamide Adenine Dinucleotide (NAD) Analogues with a Sugar Modified Nicotinamide Moiety

“…-Nicotinamide adenine dinucleotide (NAD þ ) is a cofactor in more than 400 biological redox reactions and requires the presence of enzymes such as dehydrogenases [1]. As the most important role in these reactions is played by the nicotinamide moiety, this fragment of the molecule was intensively studied.…”