CTP synthase 1

CTP synthase 1 (CTPS1) is a nucleotide biosynthetic enzyme that catalyzes the ATP-dependent amination of UTP to cytidine triphosphate (CTP), a precursor for DNA, RNA, and phospholipid synthesis (UniProt: P17812). Beyond its canonical CTP synthase activity, CTPS1 functions as a protein deamidase, modulating innate immunity through IRF3 deamidation and facilitating DNA damage responses via histone H1 deamidation. These dual enzymatic roles underscore its importance in both nucleotide metabolism and chromatin dynamics (UniProt: P17812).

CTPS1 is particularly critical for lymphocyte proliferation and immune cell activation, where increased CTP demand supports biosynthesis of nucleotides and membrane phospholipids. Mutations in CTPS1 cause Immunodeficiency 24 (IMD24; MIM 615897), characterized by impaired T and B cell proliferation and severe recurrent viral and bacterial infections (UniProt: P17812).

In Alzheimer's disease, CTPS1 is significantly downregulated in post-mortem AD brain tissue relative to age-matched controls (mean log2 fold-change: −0.38; Chaparral AD proteomics). This reduction may compromise nucleotide biosynthesis and chromatin accessibility in neurons, potentially contributing to AD pathology, though the functional consequences in neurodegeneration require further investigation.