Choline-phosphate cytidylyltransferase (CCT) (CCT)

Choline-phosphate cytidylyltransferase (CCT) is the rate-limiting enzyme in the CDP-choline (Kennedy) pathway, which is the primary route for the de novo synthesis of phosphatidylcholine (PC) in nucleated mammalian cells (UniProt P49585). It catalyzes the conversion of phosphocholine and CTP to CDP-choline, a critical precursor for PC, the most abundant phospholipid in eukaryotic membranes (PubMed: 25596343). The enzyme is regulated by a unique amphipathic helix that senses membrane lipid composition, allowing it to activate in response to low PC levels (PubMed: 11063744). Mutations in the PCYT1A gene, which encodes the alpha isoform, are associated with spondylometaphyseal dysplasia with cone-rod dystrophy (SMD-CRD) and lipodystrophy (NCBI Gene: 5130). In oncology and infectious disease, CCT is targeted by alkylphosphocholines like miltefosine, which inhibit its activity to disrupt membrane homeostasis and trigger apoptosis (PubChem CID: 3599). This enzyme's central role in lipid metabolism makes it a significant focus for understanding metabolic disorders and developing therapies for conditions characterized by aberrant membrane synthesis (PubMed: 23918313).

Other names

Phosphocholine cytidylyltransferaseCTP:phosphocholine cytidylyltransferasePCYT1Choline-phosphate cytidylyltransferase ACCT-alpha

Inhibition of the rate-limiting step in the CDP-choline pathway, leading to decreased phosphatidylcholine synthesis, disruption of membrane homeostasis, and induction of apoptosis.