Nicotinate-nucleotide pyrophosphorylase [carboxylating]

Nicotinate-nucleotide pyrophosphorylase [carboxylating] (QPRT) is a 297-amino acid enzyme involved in the catabolism of quinolinic acid, a neuroactive metabolite (UniProt: Q15274). The protein catalyzes a key step in the recycling pathway of nicotinamide adenine dinucleotide (NAD), linking tryptophan metabolism to cellular energy homeostasis in multiple tissues.

QPRT is expressed broadly across human tissues with notable relevance to neurological function, as quinolinic acid accumulation can influence synaptic plasticity and excitotoxicity in the central nervous system. The enzyme serves as a regulatory point between the kynurenine pathway and NAD biosynthesis, both implicated in neuroinflammatory and metabolic processes.

In Alzheimer's disease, QPRT is significantly upregulated in post-mortem brain tissue compared to age-matched controls, with a mean log2 fold-change of +0.86 across two subcellular fractions (Chaparral AD proteomics). This elevation suggests enhanced catabolism of quinolinic acid or compensatory NAD metabolism in AD pathology, potentially reflecting altered energy metabolism or neuroinflammatory responses characteristic of the disease.