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The Regulatory Role of NAD in Human and Animal Cells

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Abstract

Nicotinamide adenine dinucleotide (NAD) and its phosphorylated form NADP are the major coenzymes in the redox reactions of various essential metabolic pathways. NAD+ also serves as a substrate for several families of regulatory proteins, such as protein deacetylases (sirtuins), ADP-ribosyltransferases, and poly(ADP-ribose) polymerases, that control vital cell processes including gene expression, DNA repair, apoptosis, mitochondrial biogenesis, unfolded protein response, and many others. NAD+ is also a precursor for calcium-mobilizing secondary messengers. Proper regulation of these NAD-dependent metabolic and signaling pathways depends on how efficiently cells can maintain their NAD levels. Generally, mammalian cells regulate their NAD supply through biosynthesis from the precursors delivered with the diet: nicotinamide and nicotinic acid (vitamin B3), as well as nicotinamide riboside and nicotinic acid riboside. Administration of NAD precursors has been demonstrated to restore NAD levels in tissues (i.e., to produce beneficial therapeutic effects) in preclinical models of various diseases, such as neurodegenerative disorders, obesity, diabetes, and metabolic syndrome.

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Abbreviations

ADPR:

ADP-ribose

cADPR:

cyclic ADP-ribose

AIF:

apoptosis inducing factor

ARH:

ADP-ribosylhydrolase

ART:

ADP-ribosyltransferase

ARTC:

clostridial toxin-like ADP-ribosyltransferase

ARTD:

diphtheria toxin-like ADP-ribosyltransferase

ER:

endoplasmic reticulum

KDAC:

lysine deacetylase

NA:

nicotinic acid

NAAD:

nicotinic acid adenine dinucleotide

NAADP:

nicotinic acid adenine dinucleotide phosphate

Nam:

nicotinamide

NAMN:

nicotinic acid mononucleotide

NAR:

nicotinic acid riboside

NAPRT:

nicotinic acid phosphoribosyltransferase

NMN:

nicotinamide mononucleotide

NMNAT:

nicotinamide mononucleotide adenylyltransferase

NR:

nicotinamide riboside

PARP:

poly(ADP-ribose) polymerase

Sir2:

silent information regulator 2

SIRT1-7:

sirtuins 1-7

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Authors and Affiliations

  1. Institute of Cytology, Russian Academy of Sciences, 194064, St. Petersburg, Russia

    V. A. Kulikova, D. V. Gromyko & A. A. Nikiforov

  2. Peter the Great St. Petersburg Polytechnic University, 195251, St. Petersburg, Russia

    V. A. Kulikova & A. A. Nikiforov

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  1. V. A. Kulikova
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  2. D. V. Gromyko
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  3. A. A. Nikiforov
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Correspondence to A. A. Nikiforov.

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Original Russian Text © V. A. Kulikova, D. V. Gromyko, A. A. Nikiforov, 2018, published in Biokhimiya, 2018, Vol. 83, No. 7, pp. 987–1001.

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Kulikova, V.A., Gromyko, D.V. & Nikiforov, A.A. The Regulatory Role of NAD in Human and Animal Cells. Biochemistry Moscow 83, 800–812 (2018). https://doi.org/10.1134/S0006297918070040

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