Submit Papers Directly to PNAS via Track II Sign up for PNAS Online eTocs
Link: Info for AuthorsLink: Editorial BoardLink: AboutLink: SubscribeLink: AdvertiseLink: ContactLink: Sitemap Link: PNAS Home
Proceedings of the National Academy of Sciences
Link: Current Issue "" Link: Archives "" Link: Online Submission ""  Link: Advanced Search

Published online on May 8, 2006, 10.1073/pnas.0602494103
PNAS | May 16, 2006 | vol. 103 | no. 20 | 7601-7606


This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supporting Information
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via ISI Web of Science (7)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Grose, J. H.
Right arrow Articles by Roth, J. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Grose, J. H.
Right arrow Articles by Roth, J. R.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg  
What's this?

 Previous Article  | Table of Contents |  Next Article 

BIOLOGICAL SCIENCES / BIOCHEMISTRY
Evidence that feedback inhibition of NAD kinase controls responses to oxidative stress

Julianne H. Grose*,{dagger}, Lisa Joss{ddagger}, Sidney F. Velick{ddagger},§, and John R. Roth*,¶

*Department of Biology, University of Utah, Salt Lake City, UT 84112; {ddagger}Department of Biochemistry, University of Utah Medical School, Salt Lake City, UT 84112

Contributed by Sidney F. Velick, March 27, 2006

Formation of NADP+ from NAD+ is catalyzed by NAD kinase (NadK; EC 2.7.1.23 [EC] ). Evidence is presented that NadK is the only NAD kinase of Salmonella enterica and is essential for growth. NadK is inhibited allosterically by NADPH and NADH. Without effectors, NadK exists as an equilibrium mixture of dimers and tetramers (KD = 1.0 ± 0.8 mM) but is converted entirely to tetramers in the presence of the inhibitor NADPH. Comparison of NadK kinetic parameters with pool sizes of NADH and NADPH suggests that NadK is substantially inhibited during normal growth and, thus, can increase its activity greatly in response to temporary drops in the pools of inhibitory NADH and NADPH. The primary inhibitor is NADPH during aerobic growth and NADH during anaerobic growth. A model is proposed in which variation of NadK activity is central to the adjustment of pyridine nucleotide pools in response to changes in aeration, oxidative stress, and UV irradiation. It is suggested that each of these environmental factors causes a decrease in the level of reduced pyridine nucleotides, activates NadK, and increases production of NADP(H) at the expense of NAD(H). Activation of NadK may constitute a defensive response that resists loss of protective NADPH.

NAD metabolism | pyridine nucleotides | metabolic control | NADP synthesis | sedimentation equilibrium

{dagger}Present address: Department of Biochemistry, University of Utah Medical School, Salt Lake City, UT 84112.

Author contributions: J.H.G., S.F.V., and J.R.R. designed research; J.H.G. and L.J. performed research; L.J. contributed new reagents/analytic tools; J.H.G., S.F.V., and J.R.R. analyzed data; and J.H.G. and J.R.R. wrote the paper.

Conflict of interest statement: No conflicts declared.

§To whom correspondence may be sent at the present address: 2514 South Elizabeth Street, Apartment 6, Salt Lake City, UT 84106. E-mail: sfvelick{at}comcast.net

To whom correspondence may be sent at the present address: Section of Microbiology, College of Biological Sciences, University of California, Davis, CA 95616. E-mail: jrroth{at}ucdavis.edu

© 2006 by The National Academy of Sciences of the USA


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg    What's this?


This article has been cited by other articles in HighWire Press-hosted journals:


Home page
 J. Biol. Chem.Home page
G. Poncet-Montange, L. Assairi, S. Arold, S. Pochet, and G. Labesse
NAD Kinases Use Substrate-assisted Catalysis for Specific Recognition of NAD
J. Biol. Chem., November 23, 2007; 282(47): 33925 - 33934.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
N. Pollak, M. Niere, and M. Ziegler
NAD Kinase Levels Control the NADPH Concentration in Human Cells
J. Biol. Chem., November 16, 2007; 282(46): 33562 - 33571.
[Abstract] [Full Text] [PDF]

Home page
 J. Bacteriol.Home page
R. Singh, R. J. Mailloux, S. Puiseux-Dao, and V. D. Appanna
Oxidative Stress Evokes a Metabolic Adaptation That Favors Increased NADPH Synthesis and Decreased NADH Production in Pseudomonas fluorescens
J. Bacteriol., September 15, 2007; 189(18): 6665 - 6675.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
R. Woods, D. Schneider, C. L. Winkworth, M. A. Riley, and R. E. Lenski
Tests of parallel molecular evolution in a long-term experiment with Escherichia coli
PNAS, June 13, 2006; 103(24): 9107 - 9112.
[Abstract] [Full Text] [PDF]

Home page
 Sci Aging Knowl EnvironHome page
Papers of Note
Sci. Aging Knowl. Environ., May 24, 2006; 2006(9): nw9 - nw9.
[Full Text]