NAD+ kinase--a review.
NAD+ kinase catalyzes the only (known) biochemical reaction leading to the production of NADP+ from NAD+. Most evidence indicates it is found in the cytoplasm, but reports of its presence in (other) cell bodies can not be discounted. Viewed as a protein, our knowledge of NADK composition and architecture is rudimentary. Though recognized as a large multimeric protein, no agreement is evident for the molecular weight (Mr = approximately 4-65 X 10(4] of the native protein. Is calmodulin an integral subunit of (some, all) NAD+ kinases (analogous to phosphorylase kinase in skeletal muscle)? Or is it an external modulator? Consensus is evident that a subunit of molecular weight 30-35 X 10(3) is a component of the mammalian and yeast kinase. In one case (rabbit liver) two types of subunits are reported to give rise to oligomers differing in molecular weight and catalytic activities. Viewed as an enzyme it is not known why such a complex aggregate is needed for what might otherwise appear to a routine phosphorylation reaction. Rapid equilibrium random (for pigeon liver and C. utilis preparations) and ping-pong (for A. vinelandii kinase) mechanisms have been proposed for the reaction, with multiple reactant binding sites indicated for the random cases. From the perspective of enzyme modulation, the demonstration that green plant and sea urchin egg kinases are targets for calmodulin regulation by intracellular Ca2+ links NADP+ production in these sources to the multi-level discriminatory control functions inherent to this Ca2+-protein complex. Significant questions arise from the results of various investigators considered in this review. These queries offer fertile ground for the selective design of key experiments directed to a better understanding of NAD+ kinase function and pyridine nucleotide biochemistry.
McGuinness
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ET
Butler
J R
JR
D002147:Calmodulin / Q000378:metabolism; D004734:Energy Metabolism; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008027:Light; D046911:Macromolecular Substances; D008670:Metals; D008970:Molecular Weight; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010770:Phosphotransferases / Q000037:antagonists & inhibitors / Q000502:physiology*; D017853:Phosphotransferases (Alcohol Group Acceptor); D013347:Subcellular Fractions / Q000201:enzymology; D013379:Substrate Specificity
D002147:Calmodulin; D046911:Macromolecular Substances; D008670:Metals; D009243:NAD; D009249:NADP; D010770:Phosphotransferases; D017853:Phosphotransferases (Alcohol Group Acceptor); C021844:NAD kinase