A Magnesium Binding Site And The Anomeric Effect Regulate The Abiotic Redox Chemistry Of Nicotinamide Nucleotides.

Autor: Sebastianelli L; Department of Chemistry, University of Alberta, 11227 Saskatchewan Drive, Edmonton, T6G 2G2, Alberta, Canada., Kaur H; Department of Chemistry, University of Alberta, 11227 Saskatchewan Drive, Edmonton, T6G 2G2, Alberta, Canada., Chen Z; Department of Chemistry, University of Alberta, 11227 Saskatchewan Drive, Edmonton, T6G 2G2, Alberta, Canada., Krishnamurthy R; Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA., Mansy SS; Department of Chemistry, University of Alberta, 11227 Saskatchewan Drive, Edmonton, T6G 2G2, Alberta, Canada.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2024 Jun 20; Vol. 30 (35), pp. e202400411. Date of Electronic Publication: 2024 May 23.
DOI: 10.1002/chem.202400411
Abstrakt: Nicotinamide adenine dinucleotide (NAD + ) is a redox active molecule that is universally found in biology. Despite the importance and simplicity of this molecule, few reports exist that investigate which molecular features are important for the activity of this ribodinucleotide. By exploiting the nonenzymatic reduction and oxidation of NAD + by pyruvate and methylene blue, respectively, we were able to identify key molecular features necessary for the intrinsic activity of NAD + through kinetic analysis. Such features may explain how NAD + could have been selected early during the emergence of life. Simpler molecules, such as nicotinamide, that lack an anomeric carbon are incapable of accepting electrons from pyruvate. The phosphate moiety inhibits activity in the absence of metal ions but facilitates activity at physiological pH and model prebiotic conditions by recruiting catalytic Mg 2+ . Reduction proceeds through consecutive single electron transfer events. Of the derivatives tested, including nicotinamide mononucleotide, nicotinamide riboside, 3-(aminocarbonyl)-1-(2,3-dihydroxypropyl)pyridinium, 1-methylnicotinamide, and nicotinamide, only NAD + and nicotinamide mononucleotide would be capable of efficiently accepting and donating electrons within a nonenzymatic electron transport chain. The data are consistent with early metabolic chemistry exploiting NAD + or nicotinamide mononucleotide and not simpler molecules.
(© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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