Choline transport for phospholipid synthesis

Exp Biol Med (Maywood). 2006 May;231(5):490-504. doi: 10.1177/153537020623100503.

Abstract

Choline is an essential nutrient for all cells because it plays a role in the synthesis of the membrane phospholipid components of the cell membranes, as a methyl-group donor in methionine metabolism as well as in the synthesis of the neurotransmitter acetylcholine. Choline deficiency affects the expression of genes involved in cell proliferation, differentiation, and apoptosis, and it has been associated with liver dysfunction and cancer. Abnormal choline transport and metabolism have been implicated in a number of neurodegenerative disorders such as Alzheimer's and Parkinson's disease. Therefore, the study of choline transport and the characteristics of choline transporters are of central importance to understanding the mechanisms that underlie membrane integrity and cell signaling in such disorders. Kinetic studies with radiolabeled choline and inhibitors distinguish three systems for choline transport: (i) low-affinity facilitated diffusion, (ii) high-affinity, Na+-dependent transport, and (iii) intermediate-affinity, Na+-independent transport. It is only recently, however, that the proteins having transport characteristics of at least one of these systems have been identified. They include (i) polyspecific organic cation transporters (OCTs) with low affinity for choline, (ii) high-affinity choline transporters (CHT1s), and (iii) intermediate-affinity choline transporter-like (CTL1) proteins. CHT1 and CTL1 but not OCT transporters are selectively inhibited with hemicholinium-3 and essentially display characteristics of specialized transporters for targeted choline metabolism. CHT1 is abundant in neurons and almost exclusively supplies choline for acetyl-choline synthesis. The focus here is more on newly-discovered CTL1 choline transporters. They are expressed in different organisms and cell types, apparently not for the biosynthesis of acetylcholine but for the production of the most abundant metabolite of choline, the membrane lipid phosphatidylcholine.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, CD
  • Biological Transport / physiology
  • Cell Line
  • Choline / metabolism*
  • Humans
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / metabolism
  • Molecular Sequence Data
  • Organic Cation Transport Proteins / genetics
  • Organic Cation Transport Proteins / metabolism
  • Organic Cation Transporter 1 / genetics
  • Organic Cation Transporter 1 / metabolism
  • Phospholipids / biosynthesis*
  • Protein Conformation
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Sequence Alignment
  • Symporters

Substances

  • Antigens, CD
  • CTL1 protein, mouse
  • Membrane Transport Proteins
  • Organic Cation Transport Proteins
  • Organic Cation Transporter 1
  • Phospholipids
  • Protein Isoforms
  • SLC44A1 protein, human
  • SLC5A7 protein, human
  • Symporters
  • choline transporter
  • Choline