RGD Reference Report - The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways. - Rat Genome Database

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The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways.

Authors: Houtkooper, RH  Canto, C  Wanders, RJ  Auwerx, J 
Citation: Houtkooper RH, etal., Endocr Rev. 2010 Apr;31(2):194-223. doi: 10.1210/er.2009-0026. Epub 2009 Dec 9.
RGD ID: 11099972
Pubmed: PMID:20007326   (View Abstract at PubMed)
PMCID: PMC2852209   (View Article at PubMed Central)
DOI: DOI:10.1210/er.2009-0026   (Journal Full-text)

A century after the identification of a coenzymatic activity for NAD(+), NAD(+) metabolism has come into the spotlight again due to the potential therapeutic relevance of a set of enzymes whose activity is tightly regulated by the balance between the oxidized and reduced forms of this metabolite. In fact, the actions of NAD(+) have been extended from being an oxidoreductase cofactor for single enzymatic activities to acting as substrate for a wide range of proteins. These include NAD(+)-dependent protein deacetylases, poly(ADP-ribose) polymerases, and transcription factors that affect a large array of cellular functions. Through these effects, NAD(+) provides a direct link between the cellular redox status and the control of signaling and transcriptional events. Of particular interest within the metabolic/endocrine arena are the recent results, which indicate that the regulation of these NAD(+)-dependent pathways may have a major contribution to oxidative metabolism and life span extension. In this review, we will provide an integrated view on: 1) the pathways that control NAD(+) production and cycling, as well as its cellular compartmentalization; 2) the signaling and transcriptional pathways controlled by NAD(+); and 3) novel data that show how modulation of NAD(+)-producing and -consuming pathways have a major physiological impact and hold promise for the prevention and treatment of metabolic disease.

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
de novo nicotinamide adenine dinucleotide biosynthetic pathway  TAS 11099972; 11099972; 11099972; 11099972; 11099972 RGD 
de novo nicotinamide adenine dinucleotide biosynthetic pathway  ISONADSYN1 (Homo sapiens)11099972; 11099972 RGD 
de novo nicotinamide adenine dinucleotide biosynthetic pathway  ISONMNAT1 (Homo sapiens)11099972; 11099972 RGD 
de novo nicotinamide adenine dinucleotide biosynthetic pathway  ISONMNAT2 (Homo sapiens)11099972; 11099972 RGD 
de novo nicotinamide adenine dinucleotide biosynthetic pathway  ISONMNAT3 (Homo sapiens)11099972; 11099972 RGD 
de novo nicotinamide adenine dinucleotide biosynthetic pathway  ISOQPRT (Homo sapiens)11099972; 11099972 RGD 
nicotinamide adenine dinucleotide biosynthesis, the salvage pathway  TAS 11099972; 11099972; 11099972; 11099972; 11099972; 11099972; 11099972; 11099972 RGD 
nicotinamide adenine dinucleotide biosynthesis, the salvage pathway  ISONADSYN1 (Homo sapiens)11099972; 11099972 RGD 
nicotinamide adenine dinucleotide biosynthesis, the salvage pathway  ISONAMPT (Homo sapiens)11099972; 11099972 RGD 
nicotinamide adenine dinucleotide biosynthesis, the salvage pathway  ISONAPRT (Homo sapiens)11099972; 11099972 RGD 
nicotinamide adenine dinucleotide biosynthesis, the salvage pathway  ISONMNAT1 (Homo sapiens)11099972; 11099972 RGD 
nicotinamide adenine dinucleotide biosynthesis, the salvage pathway  ISONMNAT2 (Homo sapiens)11099972; 11099972 RGD 
nicotinamide adenine dinucleotide biosynthesis, the salvage pathway  ISONMNAT3 (Homo sapiens)11099972; 11099972 RGD 
nicotinamide adenine dinucleotide biosynthesis, the salvage pathway  ISONMRK1 (Homo sapiens)11099972; 11099972 RGD 
nicotinamide adenine dinucleotide biosynthesis, the salvage pathway  ISONMRK2 (Homo sapiens)11099972; 11099972 RGD 
nicotinamide adenine dinucleotide metabolic pathway   TAS 11099972 RGD 
nicotinamide adenine dinucleotide metabolic pathway   ISONNT (Homo sapiens)11099972; 11099972 RGD 
Objects Annotated

Genes (Rattus norvegicus)
Nadsyn1  (NAD synthetase 1)
Nampt  (nicotinamide phosphoribosyltransferase)
Naprt  (nicotinate phosphoribosyltransferase)
Nmnat1  (nicotinamide nucleotide adenylyltransferase 1)
Nmnat2  (nicotinamide nucleotide adenylyltransferase 2)
Nmnat3  (nicotinamide nucleotide adenylyltransferase 3)
Nmrk1  (nicotinamide riboside kinase 1)
Nmrk2  (nicotinamide riboside kinase 2)
Nnt  (nicotinamide nucleotide transhydrogenase)
Qprt  (quinolinate phosphoribosyltransferase)

Genes (Mus musculus)
Nadsyn1  (NAD synthetase 1)
Nampt  (nicotinamide phosphoribosyltransferase)
Naprt  (nicotinate phosphoribosyltransferase)
Nmnat1  (nicotinamide nucleotide adenylyltransferase 1)
Nmnat2  (nicotinamide nucleotide adenylyltransferase 2)
Nmnat3  (nicotinamide nucleotide adenylyltransferase 3)
Nmrk1  (nicotinamide riboside kinase 1)
Nmrk2  (nicotinamide riboside kinase 2)
Nnt  (nicotinamide nucleotide transhydrogenase)
Qprt  (quinolinate phosphoribosyltransferase)

Genes (Homo sapiens)
NADSYN1  (NAD synthetase 1)
NAMPT  (nicotinamide phosphoribosyltransferase)
NAPRT  (nicotinate phosphoribosyltransferase)
NMNAT1  (nicotinamide nucleotide adenylyltransferase 1)
NMNAT2  (nicotinamide nucleotide adenylyltransferase 2)
NMNAT3  (nicotinamide nucleotide adenylyltransferase 3)
NMRK1  (nicotinamide riboside kinase 1)
NMRK2  (nicotinamide riboside kinase 2)
NNT  (nicotinamide nucleotide transhydrogenase)
QPRT  (quinolinate phosphoribosyltransferase)


Additional Information