Glycerophosphocholines (GP01)

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=== Metabolism ===
=== Metabolism ===
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Phosphatidylcholine is an essential phospholipid in mammalian cells and tissues and is made in all nucleated cells via the choline pathway. Choline was first identified in ox bile in 1862. The Greek word for bile is chole. After a long interlude, in 1932, Best and Huntsman discovered the choline deficiency that results in fatty liver in rodents when insufficient choline is provided in the diet. In animals, choline can be acquired from the diet and via de novo biosynthesis: choline is produced through the methylation of phosphatidylethanolamine (PE) to phosphatidylcholine catalyzed by phosphatidylethanolamine N-methyltransferase (PEMT). Choline can then be generated from phosphatidylcholine via the action of phospholipases. The PEMT/phospholipase reactions constitute the only known endogenous pathway for choline biosynthesis in animals, whereas in plants and some microbes, choline can be made from the methylation of phosphoethanolamine. Thus, choline is made from the methylation of the ethanolamine moiety of phosphoethanolamine or PE. Both exogenous and endogenous choline is converted into phosphatidylcholine, which accounts for  95% of the total choline pool in most animal tissues. The remaining 5% includes choline, phosphocholine, glycerophosphocholine, CDP-choline, and acetylcholine. In animals, PEMT is quantitatively significant only in the liver, and it accounts for  30% of hepatic phosphatidylcholine biosynthesis in rodents. The other 70% of hepatic phosphatidylcholine is made via the choline pathway.
 
=== Enzymes/gene lists ===
=== Enzymes/gene lists ===

Revision as of 08:23, 14 August 2008


Contents

Basics

Phosphatidylcholine (PC) is a phospholipid that is a major constituent of cell membranes. Phosphatidylcholine is also known as PtdCho, 1,2-diacyl-:ussn:ue-glycero-3-phosphocholine or lecithin. It has a role in the maintenance of cell-membrane integrity and is vital to all of the basic biological processes. These are information flow that occurs within cells from DNA to RNA to proteins, the formation of cellular energy and intracellular communication or signal transduction. Phosphatidylcholine, particularly phosphatidylcholine rich in polyunsaturated fatty acids, has a marked fluidizing effect on cellular membranes. Decreased cell-membrane fluidization and breakdown of cell-membrane integrity, as well as impairment of cell-membrane repair mechanisms, are associated with a number of disorders, including liver disease, neurological diseases, various cancers and cell death.

Structure

Chemically, Phosphatidylcholine is a glycerophospholipid, built on glycerol and substituted at all three carbons. Carbons 1 and 2 are substituted by fatty acids and carbon 3 by phosphorylcholine.

Phosphatidylcholine
Phosphatidylcholine

Formula: C10H18NO8PR2

LIPID MAPS Phosphatidylcholine generic structure

Natural sources

Phosphatidylcholine

Nomenclature

Trivial - non systematic - names:

  • Phosphatidylcholine
  • Lecithin
  • 1,2-Diacyl-sn-glycero-3-phosphocholine

IUPAC

Glycerophospholipids and subclasses

Biophysical properties

Biology / biochemistry

Biochemical synthesis

Mammalian cells derive the bulk of their PC from the “Kennedy pathway” described in the work of Kennedy and coworkers almost 40 years ago that is located at the cytosolic side of the endoplasmatic reticulum. Here the first step is the phosphorylation of choline by the enzyme choline kinase (Fig. 24_2).

Figure 24_2. Kennedy Pathway
Figure 24_2. Kennedy Pathway


The formed phosphocholine is subsequently activated by a phosphate cytidylyltransferase that generates CDP-choline. Finally the enzyme choline phosphotransferase transfers the choline group of CDP-choline to diacylglycerol (DAG) which leads to the formation of PC. Alternatively, phosphatidylethanolamine (PE) is generated via the “Kennedy pathway” employing similar biochemical reaction steps. The PE thus formed can be sequentially methylated on its primary amine using S-adenosylmethionine as the methyl donor by the enzyme PE-N-Methyl-Transferase (PEMT) to form PC after the sequential transfer of 3 methyl groups. These sequential reactions are termed the PEMT pathway.

Both the phosphatidylserine and “Kennedy pathway” are found in mammalian cells but there are some tight restrictions on specific elements of the pathways. In contrast to yeast, the methylation reaction in mammalian cells is not sufficient for supplying all of the PC needed for cell growth.

Summed up, in vivo, phosphatidylcholine is produced via two major pathways. In the predominant pathway, two fatty acids are added to glycerol phosphate to generate phosphatidic acid. Next, phosphatidic acid is converted to diacylglycerol, after which phosphocholine is added on from CDPcholine. The second, minor pathway is phosphatidylethanolamine methylation, in which the phosphatidylethanolamine has three methyl groups added to its ethanolamine head-group, thereby converting it into phosphatidylcholine.

Metabolism

Enzymes/gene lists

Associated biological processes

Technology

Analysis methods

Chemical synthesis

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