CDP-choline pathway enzymes (CDP-choline pathway)

The CDP-choline pathway, also known as the Kennedy pathway, is the essential de novo biosynthetic route for phosphatidylcholine (PC), the primary structural phospholipid in mammalian cell membranes [4]. This pathway involves three key enzymes: choline kinase (CHK), which phosphorylates choline to phosphocholine; CTP:phosphocholine cytidylyltransferase (CCT), the rate-limiting enzyme that produces CDP-choline; and cholinephosphotransferase (CPT), which facilitates the final step of PC synthesis [6]. PC also serves as a critical precursor for sphingomyelin (SM) through the action of sphingomyelin synthase (SMS), which transfers the phosphocholine headgroup from PC to ceramide [7]. Dysregulation of this pathway, particularly the upregulation of choline kinase alpha (CHKA), is frequently observed in various cancers and is associated with increased cell proliferation, survival, and tumor progression [3]. Consequently, enzymes within this pathway, especially CHKA and SMS, have become attractive targets for anticancer and metabolic therapies, with inhibitors like TCD-717 and D609 demonstrating potential in preclinical and clinical settings [8, 9].

Other names

Kennedy pathwayCytidine diphosphate-choline pathwayPhosphatidylcholine biosynthetic pathway

Inhibition of de novo phosphatidylcholine synthesis and sphingomyelin production, leading to membrane disruption, depletion of signaling lipids, and induction of apoptosis [3, 8].