Choline-phosphate cytidylyltransferase A (PCYT1A)

Choline-phosphate cytidylyltransferase A (PCYT1A) is an essential, rate-limiting enzyme in the CDP-choline (Kennedy) pathway, catalyzing the conversion of phosphocholine and CTP to CDP-choline, a critical step in de novo phosphatidylcholine biosynthesis[1][2][3][4]. Phosphatidylcholine is the dominant phospholipid in eukaryotic membranes, vital for membrane integrity, cell signaling, lipid storage, and organelle function. PCYT1A is primarily localized to the nucleus and inner nuclear membrane, where it senses membrane curvature stress and regulates phosphatidylcholine homeostasis[2]. Biallelic loss-of-function mutations in PCYT1A cause a spectrum of disorders including inherited retinal dystrophies, lipodystrophy, fatty liver, and insulin resistance, sometimes through activation of cell death pathways such as ferroptosis[1][3]. The enzyme is highly expressed in metabolically active tissues, notably retina, liver, and adipose tissue, where its function is nonredundant despite the presence of alternative biosynthetic routes[1][3]. Because of its critical physiological roles, PCYT1A is regarded as an essential metabolic enzyme and a potential target for metabolic and degenerative disease research, though no direct pharmacological inhibitors or activators are currently in clinical use[1][3].

Other names

Choline-phosphate cytidylyltransferase APCYT1ACTPCTPCYT1CCT ACT ACTCCTalphaCCT-alphaCTP:phosphocholine cytidylyltransferase APhosphorylcholine transferase Aphosphate cytidylyltransferase 1, choline, alpha isoformCTP:phosphocholine cytidylyltransferase-alphacholine-phosphate cytidylyltransferase alphaphosphorylcholine transferase alphaCCTACGL5SMDCRD

Inhibition or mutation reduces phosphatidylcholine synthesis, disturbing membrane lipid composition and organelle function Loss-of-function mutations can trigger ferroptosis and fatty acid metabolic disturbances[1][3]