Structure and Function of NAD Kinase and NADP Phosphatase: Key Enzymes That Regulate the Intracellular Balance of NAD(H) and NADP(H)

Abstract

þ and NADPH) are undoubtedly significant and distinct. Hence, regulation of the intracellular balance of NAD(H) and NADP(H) is important. The key enzymes involved in the regulation are NAD kinase and NADP phosphatase. In 2000, we first succeeded in identifying the gene for NAD kinase, thereby facilitating worldwide studies of this enzyme from various organisms, including eubacteria, archaea, yeast, plants, and humans. Molecular biological study has revealed the physiological function of this enzyme, that is to say, the significance of NADP(H), in some model organisms. Structural research has elucidated the tertiary structure of the enzyme, the details of substratebinding sites, and the catalytic mechanism. Research on NAD kinase also led to the discovery of archaeal NADP phosphatase. In this review, we summarize the physiological functions, applications, and structure of NAD kinase, and the way we discovered archaeal NADP phosphatase.

Metabolome and Photochemical Analysis of Rice Plants Overexpressing Arabidopsis NAD Kinase Gene

“…NAD is highly oxidized and is involved primarily in intracellular catabolic reactions, whereas NADP is predominantly found in its reduced form and participates in anabolic reactions and defense against oxidative stress (Ziegler, 2000;Noctor et al, 2006;Pollak et al, 2007a). Since NAD(H) and NADP(H) play a variety of distinct physiological roles, the regulation of the NAD(H)/ NADP(H) balance is essential for cell survival (Kawai and Murata, 2008;Hashida et al, 2009).One of the key enzymes that regulates NAD(H)/ NADP(H) balance is NAD kinase (NADK; EC 2.7.1.23), which catalyzes NAD phosphorylation in the presence of ATP. The genes encoding NADK were cloned recently from all organisms investigated to date, except for Chlamydia trachomatis (Kawai and Murata, 2008).…”

“…Since NAD(H) and NADP(H) play a variety of distinct physiological roles, the regulation of the NAD(H)/ NADP(H) balance is essential for cell survival (Kawai and Murata, 2008;Hashida et al, 2009).…”

“…The genes encoding NADK were cloned recently from all organisms investigated to date, except for Chlamydia trachomatis (Kawai and Murata, 2008). Only a single gene encoding NADK has been found in some bacteria and mammals (Kawai and Murata, 2008). In contrast, NADK activity was detected in not only the cytosol but also organelles in yeast and plant (Jarrett et al, 1982;Simon et al, 1982;Dieter and Marme, 1984;, and three genes including cytosol-type and organelle-type NADK have been cloned in yeast (Kawai et al, 2001;Outten and Culotta, 2003) and plants (Turner et al, 2004(Turner et al, , 2005.…”

“…NAD is highly oxidized and is involved primarily in intracellular catabolic reactions, whereas NADP is predominantly found in its reduced form and participates in anabolic reactions and defense against oxidative stress (Ziegler, 2000;Noctor et al, 2006;Pollak et al, 2007a). Since NAD(H) and NADP(H) play a variety of distinct physiological roles, the regulation of the NAD(H)/ NADP(H) balance is essential for cell survival (Kawai and Murata, 2008;Hashida et al, 2009).…”

“…The genes encoding NADK were cloned recently from all organisms investigated to date, except for Chlamydia trachomatis (Kawai and Murata, 2008). Only a single gene encoding NADK has been found in some bacteria and mammals (Kawai and Murata, 2008).…”