2018
DOI: 10.1038/s41591-018-0138-z
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De novo NAD+ biosynthetic impairment in acute kidney injury in humans

Abstract: Nicotinamide adenine dinucleotide (NAD) extends longevity in experimental organisms, raising interest in its impact on human health. De novo NAD biosynthesis from tryptophan is evolutionarily conserved yet considered supplanted among higher species by biosynthesis from nicotinamide (NAM). Here we show that a bottleneck enzyme in de novo biosynthesis, quinolinate phosphoribosyltransferase (QPRT), defends renal NAD and mediates resistance to acute kidney injury (AKI). Following murine AKI, renal NAD fell, quinol… Show more

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Cited by 284 publications
(262 citation statements)
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“…Poyan Mehr et al. suggested that low levels of NAD + in AKI are associated with the diminished activity of quinolinate phosphoribosyltransferase, an enzyme associated with NAD + synthesis from tryptophan [55]. These studies have helped to elucidate the role of NAD + deficiency in kidney disease development.…”
Section: Discussionmentioning
confidence: 99%
“…Poyan Mehr et al. suggested that low levels of NAD + in AKI are associated with the diminished activity of quinolinate phosphoribosyltransferase, an enzyme associated with NAD + synthesis from tryptophan [55]. These studies have helped to elucidate the role of NAD + deficiency in kidney disease development.…”
Section: Discussionmentioning
confidence: 99%
“…Additional recent metabolomic studies in a mouse model of ischemic AKI have identified a deficiency in the urinary and intra-renal nicotinamide adenine dinucleotide (NAD), an essential component of energy generation via glycolysis and the Kreb's cycle (12). In a phase I study of oral NAM supplementation (which generates NAD via a salvage pathway) in adults undergoing cardiac surgery, the rise in serum creatinine was prevented compared to placebo (12). Additional studies are underway.…”
Section: The Unanticipated Heterogeneity Of Acute Kidney Injurymentioning
confidence: 99%
“…These modified proteins contribute to regulating Ca 2+ signaling, chromatin structure, DNA repair, circadian rhythm, metabolic responses, and lifespan [1][2][3][4][5]. Several human diseases have been associated with aberrant NAD + metabolism, including diabetes, cancer, and neuron degeneration [2,3,[5][6][7][8][9][10][11][12]. Administration of NAD + precursors such as nicotinamide (NAM), nicotinamide mononucleotide (NMN), nicotinic acid riboside (NaR), and nicotinamide riboside (NR) has been shown to increase NAD + levels and ameliorate associated deficiencies in various model systems including human cells [3,[5][6][7][8][9][10][11][13][14][15][16].…”
Section: Introductionmentioning
confidence: 99%
“…Several human diseases have been associated with aberrant NAD + metabolism, including diabetes, cancer, and neuron degeneration [2,3,[5][6][7][8][9][10][11][12]. Administration of NAD + precursors such as nicotinamide (NAM), nicotinamide mononucleotide (NMN), nicotinic acid riboside (NaR), and nicotinamide riboside (NR) has been shown to increase NAD + levels and ameliorate associated deficiencies in various model systems including human cells [3,[5][6][7][8][9][10][11][13][14][15][16]. Nicotinic acid (NA) (niacin, vitamin B3) was first identified as a "Pellagra-preventive factor" in studies pioneered by Goldberger and Elvehjem in the early 1900s [17][18][19].…”
Section: Introductionmentioning
confidence: 99%