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Title: Mechanistic studies of the base-catalyzed hydrolysis of pyridine nucleotides

Abstract

The pH dependence of base-catalyzed hydrolysis of ..beta..-NAD has been determined over the range from pH 8.5 to 13.5. Below pH 10.5 the reaction rate constant is linearly dependent on hydroxide concentration whereas above pH 12.5 the reaction becomes pH independent. A nonlinear least squares fit of the data yields a pK/sub a/ of 12.2, corresponding to the ionization of the 2'-OH of the nicotinamide ribose as determined by /sup 1/H and /sup 13/C NMR. Based on these data, as well as solvent isotope effects and data from previous investigators, the authors propose that ionization of the ribose diol stabilizes an oxonium ion intermediate, thus, facilitating S/sub N/1 hydrolysis of the nicotinamide-glycosyl bond with release of nicotinamide. Further evidence for this mechanism is provided by investigation of the 2',3'-O-isopropylidine nicotinamide riboside. This compound is found to be highly resistant to hydrolysis in base and product analysis by NMR reveals that only 2-hydroxy-3-pyridinecarboxaldehyde is released. The influence on the reaction rate and mechanism resulting from other modifications of the sugar moiety of nicotinamide nucleosides are discussed.

Authors:
; ; ; ;
Publication Date:
Research Org.:
Univ. of California, San Francisco
OSTI Identifier:
5334515
Report Number(s):
CONF-8606151-
Journal ID: CODEN: FEPRA; TRN: 86-031403
Resource Type:
Conference
Journal Name:
Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
Additional Journal Information:
Journal Volume: 45:6; Conference: 76. annual meeting of the Federation of American Society for Experimental Biology, Washington, DC, USA, 8 Jun 1986
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 62 RADIOLOGY AND NUCLEAR MEDICINE; NAD; HYDROLYSIS; BIOCHEMICAL REACTION KINETICS; CARBON 13; CATALYSIS; ISOTOPE EFFECTS; LEAST SQUARE FIT; NICOTINAMIDE; NMR SPECTRA; NUCLEAR MAGNETIC RESONANCE; NUCLEOSIDES; PH VALUE; RIBOSE; ALDEHYDES; AMIDES; AZINES; CARBOHYDRATES; CARBON ISOTOPES; CHEMICAL REACTIONS; COENZYMES; DECOMPOSITION; EVEN-ODD NUCLEI; HETEROCYCLIC COMPOUNDS; ISOTOPES; KINETICS; LIGHT NUCLEI; LYSIS; MAGNETIC RESONANCE; MAXIMUM-LIKELIHOOD FIT; MONOSACCHARIDES; NUCLEI; NUCLEOTIDES; NUMERICAL SOLUTION; ORGANIC COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; PENTOSES; PYRIDINES; REACTION KINETICS; RESONANCE; RIBOSIDES; SACCHARIDES; SOLVOLYSIS; SPECTRA; STABLE ISOTOPES; VITAMIN B GROUP; VITAMINS; 550201* - Biochemistry- Tracer Techniques; 550600 - Medicine

Citation Formats

Johnson, R W, Marschner, T M, Malver, O, Sleath, P R, and Oppenheimer, N J. Mechanistic studies of the base-catalyzed hydrolysis of pyridine nucleotides. United States: N. p., 1986. Web.
Johnson, R W, Marschner, T M, Malver, O, Sleath, P R, & Oppenheimer, N J. Mechanistic studies of the base-catalyzed hydrolysis of pyridine nucleotides. United States.
Johnson, R W, Marschner, T M, Malver, O, Sleath, P R, and Oppenheimer, N J. 1986. "Mechanistic studies of the base-catalyzed hydrolysis of pyridine nucleotides". United States.
@article{osti_5334515,
title = {Mechanistic studies of the base-catalyzed hydrolysis of pyridine nucleotides},
author = {Johnson, R W and Marschner, T M and Malver, O and Sleath, P R and Oppenheimer, N J},
abstractNote = {The pH dependence of base-catalyzed hydrolysis of ..beta..-NAD has been determined over the range from pH 8.5 to 13.5. Below pH 10.5 the reaction rate constant is linearly dependent on hydroxide concentration whereas above pH 12.5 the reaction becomes pH independent. A nonlinear least squares fit of the data yields a pK/sub a/ of 12.2, corresponding to the ionization of the 2'-OH of the nicotinamide ribose as determined by /sup 1/H and /sup 13/C NMR. Based on these data, as well as solvent isotope effects and data from previous investigators, the authors propose that ionization of the ribose diol stabilizes an oxonium ion intermediate, thus, facilitating S/sub N/1 hydrolysis of the nicotinamide-glycosyl bond with release of nicotinamide. Further evidence for this mechanism is provided by investigation of the 2',3'-O-isopropylidine nicotinamide riboside. This compound is found to be highly resistant to hydrolysis in base and product analysis by NMR reveals that only 2-hydroxy-3-pyridinecarboxaldehyde is released. The influence on the reaction rate and mechanism resulting from other modifications of the sugar moiety of nicotinamide nucleosides are discussed.},
doi = {},
url = {https://www.osti.gov/biblio/5334515}, journal = {Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)},
number = ,
volume = 45:6,
place = {United States},
year = {Thu May 01 00:00:00 EDT 1986},
month = {Thu May 01 00:00:00 EDT 1986}
}

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