Activity of NMN⁺, nicotinamide ribose and analogs in alcohol oxidation promoted by horse‐liver alcohol dehydrogenase

Abstract

Kinetic constants of horse-liver alcohol-dehydrogenase-mediated oxidation of alcohol by nicotinamide mononucleotide and nicotinamide ribose were determined and the role of different adenine moieties complementing the reaction mixtures was investigated. Five nicotinamide ribose analogs were synthesized and their activities as NAD' inhibitors and as cofactors in this dehydrogenase-mediated oxidation of alcohol were assayed. In the light of these results, structural requirements of the pyridine ribofuranosyl part of the NAD' are discussed.In a recent work, we have shown that the enzymatic activity of horse-liver alcohol dehydrogenase (HLADH), an NAD' -requiring enzyme, was partly retained when NMN+ or the nicotinamide ribose (NR') were used as cofactors. Moreover, the efficiencies of these NAD' fragments were strongly improved when the medium was supplemented with adenosine and AMP respectively [I].Many NAD + analogs [2] have been synthesized with, in particular, the nicotinamide-linked ribofuranosyl residue substituted by linear alkyl groups and assayed as cofactors. Only the analog with the butyl group was found to be slightly active, showing the importance of the nicotinamide-linked ri bofuranosyl.We describe in the present work the synthesis of four N R + analogs I -IV, where a cyclopentane diversely substituted is attached to the nicotinamide moiety, and one nicotinamide derivative V, where the nitrogen atom is substituted by a C 5 chain possessing four hydroxyl groups. We also describe the abilities of these derivatives to function as cofactors with HLADH and, in order tentatively to elucidate how adenosine and AMP activate the functional fragments, we present some kinetic studies of the enzymatic reactions. MATERIALS AND METHODSNMN' and NR' were prepared and purified according to [I] and [3] respectively. HLADH was from Sigma; NAD', ADP, AMP and adenosine were from Fluka.The enzyme kinetics were carried out in a 1-ml ultraviolet

Carbanicotinamide adenine dinucleotide: synthesis and enzymological properties of a carbocyclic analog of oxidized nicotinamide adenine dinucleotide

“…Evaporation of the solvent resulted in the isolation of 1.22 g (4.24 mmol, 52% of theory) of 4 as a colorless, amorphous solid; and 13C NMR are reported in Tables I and II. *H NMR is an agreement with that reported for this compound by Sicsic et al (1986). Fast atom bombardment mass spectrum.…”

The Hetero Diels−Alder Reactions between d-Mannose-Derived Halonitroso Compounds and Cyclopentadiene: Scope and Limitations

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Synthetic Biomimetic Coenzymes and Alcohol Dehydrogenases for Asymmetric Catalysis

“…These examples are important steps towards the use of NCBs with dehydrogenases, and more specifically ADHs, which would be advantageous for large scale applications, although NCB recycling and stability is still in its early stages [36]. In a previous study, cofactors NR, NMN, and carbocyclic analogues showed no observable activity in the HLADH-catalyzed oxidation of ethanol [37,38], corroborated by computational studies on the mechanism for hydride transfer in HLADH [39].…”