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, quinolinate rose, and QPRT declined. QPRT^+/- mice exhibited higher quinolinate, lower NAD⁺, and higher AKI susceptibility. Metabolomics suggested an elevated urinary quinolinate/tryptophan ratio (uQ/T) as an indicator of

SUBMITTER: Poyan Mehr A 

PROVIDER: S-EPMC6129212 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature