Choline: Definition, Synthesis, Absorption, Transport, and Distribution

Choline was discovered in 1864 by the German chemist Adolph Friedrich Ludwig Strecker.It is an essential nutrient, i.e., necessary for life.It belongs to the quaternary amines (2-hydroxyethyl-N, N, N-trimethylammonium) and is present in the diet in free and esterified forms. Choline can be synthesized by the human organism itself, but in many cases the amount is insufficient to meet the need, so additional dietary intake of choline is necessary.It is most commonly found in foods free or as components of the following compounds: Phosphatidyl choline (lecithin), phosphocholine, glycerophosphocholine and sphingomyelin.Sphingomyelin and phosphatidyl choline (PC) are fat soluble and the free choline, phosphocholine as well as glycerophosphocholine are water soluble. It is less abundant in foods in the form of cytidine-5-diphosphate choline and acetylcholine.The essential nutrient choline and its metabolites play an essential role in many physiological processes:

  • Membrane structure and functions.
  • Methyl group metabolism
  • Metabolism and transport of lipids and cholesterol.
  • Neurotransmission

In 2016, the European Food Safety Authority (EFSA) established an adequate intake level of 400 mg/day for adults. They justified this based on the average intake of choline by healthy people in the European Union as well as the intake amount needed to correct deficiency symptoms.SynthesisCholine can be synthesized in the human body through several pathways:

  • By methylation of phosphatidylethanolamine via the hepatic phosphatidylethanolamine N-methyltransferase pathway.
  • By hydrolysis of phosphatidyl choline formed via the cytidine-5-diphosphate (CDP)-choline pathway.

AbsorptionFree choline is rapidly absorbed by enterocytes (hem cells; by far the most abundant cell of the small intestinal epithelium), with the help of saturable organic cation transporters (OCTs). These use the mechanism of facilitated diffusion and are thus influenced by choline concentration and electrical potential across the membrane.Phosphatidyl choline ingested through the diet causes the concentration of free choline to increase in plasma for 8-12 hours without significantly increasing phosphatidyl choline concentration.Phosphocholine and glycerophosphocholine are rapidly absorbed and are found in plasma predominantly in the form of free choline. However, the water-soluble substances phosphocholine and glycerophosphocholine can also enter the portal circulation of the liver unchanged. Fat-soluble forms of choline, such as phosphatidyl choline and sphingomyelin, on the other hand, must be hydrolyzed (cleavage of a compound by reaction with water) by phospholipases (enzymes that cleave phospholipids and other lipophilic substances) to release the choline or pass into the lymph (aqueous pale yellow fluid contained in the lymphatic vessels) enclosed in chylomicrons (lipoprotein particles). TransportFree choline is transported in the aqueous phase of plasma, whereas phosphorylated compounds are bound to or transported as a component of lipoproteins (complexes of proteins (apolipoproteins), cholesterol, triglycerides, and phospholipids).Free choline, being a charged hydrophilic cation, must pass through biological membranes via transport mechanisms. Three forms are known to date.Stored choline is either as a phospholipid in membranes or intracellularly (“inside the cell”) as phosphatidyl choline as well as glycerophosphocholine.