Back to Search Start Over

Metabolic Alterations in NADSYN1-Deficient Cells.

Authors :
Meijer NWF
Gerrits J
Zwakenberg S
Zwartkruis FJT
Verhoeven-Duif NM
Jans JJM
Source :
Metabolites [Metabolites] 2023 Dec 12; Vol. 13 (12). Date of Electronic Publication: 2023 Dec 12.
Publication Year :
2023

Abstract

NAD synthetase 1 (encoded by the gene NADSYN1) is a cytosolic enzyme that catalyzes the final step in the biosynthesis of nicotinamide adenine dinucleotide (NAD+) from tryptophan and nicotinic acid. NADSYN1 deficiency has recently been added to the spectrum of congenital NAD+ deficiency disorders. To gain insight into the metabolic consequences of NADSYN1 deficiency, the encoding gene was disrupted in A549 and HEK293T cells, and the metabolome was profiled in the presence of different NAD+ precursors, including tryptophan, nicotinamide and nicotinic acid. We demonstrate that when precursors of the NAD+ salvage pathway in the form of nicotinamide become limiting, NADSYN1 deficiency results in a decline in intracellular NAD+ levels even in the presence of other potential NAD+ sources such as tryptophan and nicotinic acid. As a consequence, alterations in 122 and 69 metabolites are observed in NADSYN1-deficient A549 and HEK293T cells compared to the wild-type cell line (FC > 2 and p < 0.05). We thus show that NADSYN1 deficiency results in a metabolic phenotype characterized by alterations in glycolysis, the TCA cycle, the pentose phosphate pathway, and the polyol pathway.

Details

Language :
English
ISSN :
2218-1989
Volume :
13
Issue :
12
Database :
MEDLINE
Journal :
Metabolites
Publication Type :
Academic Journal
Accession number :
38132878
Full Text :
https://doi.org/10.3390/metabo13121196