Journal of Biological Chemistry
Volume 286, Issue 48, 2 December 2011, Pages 41246-41252
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Enzymology
Extremely Conserved ATP- or ADP-dependent Enzymatic System for Nicotinamide Nucleotide Repair*

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The reduced forms of NAD and NADP, two major nucleotides playing a central role in metabolism, are continuously damaged by enzymatic or heat-dependent hydration. We report the molecular identification of the eukaryotic dehydratase that repairs these nucleotides and show that this enzyme (Carkd in mammals, YKL151C in yeast) catalyzes the dehydration of the S form of NADHX and NADPHX, at the expense of ATP, which is converted to ADP. Surprisingly, the Escherichia coli homolog, YjeF, a bidomain protein, catalyzes a similar reaction, but using ADP instead of ATP. The latter reaction is ascribable to the C-terminal domain of YjeF. This represents an unprecedented example of orthologous enzymes using either ADP or ATP as phosphoryl donor. We also show that eukaryotic proteins homologous to the N-terminal domain of YjeF (apolipoprotein A-1-binding protein (AIBP) in mammals, YNL200C in yeast) catalyze the epimerization of the S and R forms of NAD(P)HX, thereby allowing, in conjunction with the energy-dependent dehydratase, the repair of both epimers of NAD(P)HX. Both enzymes are very widespread in eukaryotes, prokaryotes, and archaea, which together with the ADP dependence of the dehydratase in some species indicates the ancient origin of this repair system.

Enzyme Kinetics
Enzyme Purification
Enzymes
Metabolism
NADH

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*

This work was supported by the Fonds de la Recherche Scientifique (FRS-FNRS), by the European Union Seventh Framework Programme (Grant FP7/2007-2013) under Grant Agreement 276814, and by Welbio (Walloon region).

The on-line version of this article (available at http://www.jbc.org) contains supplemental Experimental Procedures, Tables S1–S3, and Figs. S1–S5.

1

Collaborateur Logistique of the FRS-FNRS.