Quinolinate phosphoribosyltransferase (QPRT) (QPRT)

Quinolinate phosphoribosyltransferase (QPRT) is a critical enzyme in the kynurenine pathway, responsible for the de novo synthesis of nicotinamide adenine dinucleotide (NAD+) from tryptophan (UniProt P60484). It catalyzes the conversion of quinolinic acid (QA), a potent endogenous NMDA receptor agonist and neurotoxin, into nicotinic acid mononucleotide (NaMN). In the context of oncology, QPRT is often upregulated in aggressive tumors such as glioblastoma, where it supports metabolic demands and confers resistance to radiotherapy and chemotherapy by maintaining NAD+ levels (PubMed: 23412382). Conversely, in neurodegenerative disorders like Huntington's disease, impaired QPRT activity can lead to the toxic accumulation of quinolinic acid, contributing to neuronal death (PubMed: 30256711). Therapeutic strategies targeting QPRT include the use of small molecule inhibitors to sensitize cancer cells or RNA-based therapies to modulate its expression. Monitoring QPRT levels and its substrate, quinolinic acid, serves as a potential biomarker for disease progression and therapeutic response. The enzyme also plays a protective role in acute kidney injury by maintaining NAD+ levels in renal tubular cells (PubMed: 30135444).

Other names

QPRTaseNicotinate-nucleotide pyrophosphorylase [carboxylating]Quinolinate phosphoribosyltransferase (decarboxylating)

Competitive inhibition of enzyme activity or reduction of protein expression via RNA interference (siRNA/ASO).