The Kennedy pathway—De novo synthesis of phosphatidylethanolamine and phosphatidylcholine

Abstract

SummaryThe glycerophospholipids phosphatidylcholine (PC) and phosphatidylethanolamine (PE) account for greater than 50% of the total phospholipid species in eukaryotic membranes and thus play major roles in the structure and function of those membranes. In most eukaryotic cells, PC and PE are synthesized by an aminoalcoholphosphotransferase reaction, which uses sn-1,2-diradylglycerol and either CDP-choline or CDP-ethanolamine, respectively. This is the last step in a biosynthetic pathway known as the Kennedy pathway, so named after Eugene Kennedy who elucidated it over 50 years ago. This review will cover various aspects of the Kennedy pathway including: each of the biosynthetic steps, the functions and roles of the phospholipid products PC and PE, and how the Kennedy pathway has the potential of being a chemotherapeutic target against cancer and various infectious diseases. IUBMBIUBMB Life, 62(6): [414][415][416][417][418][419][420][421][422][423][424][425][426][427][428] 2010

Mutations disrupting the Kennedy phosphatidylcholine pathway in humans with congenital lipodystrophy and fatty liver disease

“…1 F.P., K.L., and A.G. contributed equally to this work. 2 To whom correspondence may be addressed. E-mail: so104@medschl.cam.ac.uk, ib1@ sanger.ac.uk, or dbs23@medschl.cam.ac.uk.…”

“…1A): choline kinase phosphorylates choline before choline phosphate cytidylyltransferase 1 α (encoded by the PCYT1A gene) generates the high-energy donor CDP-choline in the rate-limiting step of the pathway. In the last step, DAG:CDP-choline cholinephosphotransferase (CPT) uses CDP-choline and diacylglycerol (DAG) to form PC (2,3).…”

The serpentine path to a novel mechanism-based inhibitor of acute inflammatory lung injury

“…DPPC, the major bioactive phospholipid component of lung surfactant, can be synthesized by two well-described pathways. The first called the de novo (Kennedy) pathway requires the essential nutrient, choline, that is phosphorylated and, following additional processing, interacts with dipalmitoyl glycerophosphate to form DPPC (41). The second pathway, called the remodeling pathway (Lands cycle), results in the remodeling of phosphatidylcholine (PC), most commonly a PC containing an unsaturated fatty acid in the sn-2 position, to generate the disaturated lipid (54).…”

Role of phosphatidylserine synthase in shaping the phospholipidome of Candida albicans

“…Although PI, PG and PS can be end products, PG and PS can be further modified to form CL and PE, respectively, and PE can subsequently be methylated to produce PC. Candida albicans also utilizes exogenously provided ethanolamine and choline to produce PE and PC, respectively, via the Kennedy pathway (Gibellini and Smith 2010;Chen et al 2010b;Henry, Kohlwein and Carman 2012).…”