Phosphate cytidylyltransferase 1, choline-alpha (PCYT1A)

Phosphate cytidylyltransferase 1, choline-alpha (PCYT1A) is the rate-limiting enzyme in the Kennedy (CDP-choline) pathway, which is the primary route for the de novo synthesis of phosphatidylcholine (PC), the most abundant phospholipid in eukaryotic membranes (UniProt P49585; PMID: 29754800). The enzyme exists in an inactive cytosolic form and an active membrane-bound form, with its activity regulated by membrane lipid composition and phosphorylation (PMID: 8155650). PCYT1A plays a critical role in maintaining cellular membrane integrity, lipid droplet biogenesis, and signaling processes related to cell growth and survival (PMID: 30146204). Mutations in the PCYT1A gene are linked to several rare genetic disorders, including spondylometaphyseal dysplasia with cone-rod dystrophy (SMD-CRD) and congenital generalized lipodystrophy, highlighting its essential role in skeletal and adipose tissue development (PMID: 24889615). In oncology, PCYT1A is often upregulated by oncogenes like MYC to support the high metabolic demands of rapidly proliferating tumor cells, making it a potential therapeutic target in cancers such as diffuse large B-cell lymphoma (PMID: 28686226). Experimental inhibitors and natural compounds like berberine have shown efficacy in modulating PCYT1A activity to induce necroptosis or ferroptosis in diseased cells (PMID: 28686226; PMID: 38115345).

Other names

Choline-phosphate cytidylyltransferase ACTP:phosphocholine cytidylyltransferase alphaCCT-alphaCT-alphaCCTAPhosphorylcholine transferase ASMDCRDCGL5

Drugs targeting this enzyme typically act by inhibiting its expression (e.g., Berberine via MYC inhibition) or by directly modulating its catalytic activity as substrate analogs or allosteric regulators to control phosphatidylcholine levels.