## Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

## If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

# Evidence That Feedback Inhibition of NAD Kinase Controls Responses to Oxidative Stress

Julianne H. Grose, Lisa Joss, Sidney F. Velick and John R. Roth
Proceedings of the National Academy of Sciences of the United States of America
Vol. 103, No. 20 (May 16, 2006), pp. 7601-7606
Stable URL: http://www.jstor.org/stable/30049303
Page Count: 6
Preview not available

## Abstract

Formation of NADP⁺ from NAD⁺ is catalyzed by NAD kinase (NadK; EC 2.7.1.23). 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 ($K_{D} = 1.0 \pm 0.8 mM$) 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.

• 7601
• 7602
• 7603
• 7604
• 7605
• 7606