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Nicotinamide/nicotinic acid mononucleotide adenylyltransferase, new insights into an ancient enzyme

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Abstract

Nicotinamide/nicotinic acid mononucleotide adenylyltransferase (NMNAT) has long been known as the master enzyme in NAD biosynthesis in living organisms. A burst of investigations on NMNAT, going beyond enzymology, have paralleled increasing discoveries of key roles played by NAD homeostasis in a number or patho-physiological conditions. The availability of in-depth kinetics and structural enzymology analyses carried out on NMNATs from different organisms offer a powerful tool for uncovering fascinating evolutionary relationships. On the other hand, additional functions featuring NMNAT have emerged from investigations aimed at unraveling the molecular mechanisms responsible for complex biological phenomena such as neurodegeneration. NMNAT appears to be a multifunctional protein that sits both at the core of central metabolism and at a crossroads of multiple cellular processes. The resultant wealth of biochemical data has built a robust framework upon which design of NMNAT activators, inhibitors or enzyme variants of potential medical interest can be based.

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Abbreviations

NAD:

Nicotinamide adenine dinucleotide

NaAD:

Nicotinic acid adenine dinucleotide

NMN:

Nicotinamide mononucleotide

NaMN:

Nicotinic acid mononucleotide

NmR:

Nicotinamide ribose

AMP-CPP:

Alpha, beta-methyleneadenosine 5′-triphosphate

NLS:

Nuclear localization signal

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Acknowledgements

This work was supported by funding to M.R. from Regione Piemonte (Ricerca Applicata, CIPE 2004) and MIUR (PRIN 2007), and to R.G.Z. from the Florida Biomedical Research Program (Florida, USA) and the Neuroscience Center at the University of Miami, Miller School of Medicine.

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  1. Department of Molecular and Cellular Pharmacology, Neuroscience Center, Miller School of Medicine, University of Miami, Miami, FL, 33136, USA

    Rong Grace Zhai

  2. DiSCAFF, University of Piemonte Orientale “A. Avogadro”, Via Bovio, 6, 28100, Novara, Italy

    Menico Rizzi & Silvia Garavaglia

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  1. Rong Grace Zhai
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Correspondence to Rong Grace Zhai or Menico Rizzi.

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Zhai, R.G., Rizzi, M. & Garavaglia, S. Nicotinamide/nicotinic acid mononucleotide adenylyltransferase, new insights into an ancient enzyme. Cell. Mol. Life Sci. 66, 2805–2818 (2009). https://doi.org/10.1007/s00018-009-0047-x

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