Failure to repair damaged NAD(P)H blocks de novo serine synthesis in human cells.

ABSTRACT:

Background

Metabolism is error prone. For instance, the reduced forms of the central metabolic cofactors nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH), can be converted into redox-inactive products, NADHX and NADPHX, through enzymatically catalyzed or spontaneous hydration. The metabolite repair enzymes NAXD and NAXE convert these damaged compounds back to the functional NAD(P)H cofactors. Pathogenic loss-of-function variants in NAXE and NAXD lead to development of the neurometabolic disorders progressive, early-onset encephalopathy with brain edema and/or leukoencephalopathy (PEBEL)1 and PEBEL2, respectively.

Methods

To gain insights into the molecular disease mechanisms, we investigated the metabolic impact of NAXD deficie

SUBMITTER: Walvekar AS 

PROVIDER: S-EPMC11715087 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature