From yeast to humans - roles of the Kennedy pathway for phosphatidylcholine synthesis

FEBS Lett. 2018 Apr;592(8):1256-1272. doi: 10.1002/1873-3468.12919. Epub 2017 Dec 19.

Abstract

The major phospholipid present in most eukaryotic membranes is phosphatidylcholine (PC), comprising ~ 50% of phospholipid content. PC metabolic pathways are highly conserved from yeast to humans. The main pathway for the synthesis of PC is the Kennedy (CDP-choline) pathway. In this pathway, choline is converted to phosphocholine by choline kinase, phosphocholine is metabolized to CDP-choline by the rate-determining enzyme for this pathway, CTP:phosphocholine cytidylyltransferase, and cholinephosphotransferase condenses CDP-choline with diacylglycerol to produce PC. This Review discusses how PC synthesis via the Kennedy pathway is regulated, its role in cellular and biological processes, as well as diseases known to be associated with defects in PC synthesis. Finally, we present the first model for the making of a membrane via PC synthesis.

Keywords: membrane; phosphatidylcholine; phospholipid.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Choline Kinase / genetics
  • Choline Kinase / metabolism*
  • Cytidine Diphosphate Choline / genetics
  • Cytidine Diphosphate Choline / metabolism*
  • Humans
  • Phosphatidylcholines / biosynthesis*
  • Phosphatidylcholines / genetics
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Phosphatidylcholines
  • Saccharomyces cerevisiae Proteins
  • Cytidine Diphosphate Choline
  • Choline Kinase