While the presence of phosphorus in brain tissue was first reported in 1719 by Hensing JT (Professor of medicine et the University of Giessen), its presence in lipids extracted from brain with ethanol  was discovered in 1811 by Vauquelin. This famous French chemist (1763-1829) which discovered also chromium and beryllium in 1797, was professor in the most famous institutions of his time. Vauquelin took Chevreul in his laboratory at the Muséum d’Histoire Naturelle in 1803 to study organic materials

Several chemists isolated similar substances from brain in hot alcohol which were named matière blanche, cérébrote, acide cérébrique or oleophosphoric acid. Later, another French chemist, Gobley, isolated from egg-yolk and brain a phosphorus-containing lipid and named it lecithin (from the greek lecithos, egg-yolk) (now phosphatidylcholine). He showed in 1850 than glycerophosphoric acid could be prepared from lecithin (J Pharm Chim 1850, 17, 401) while Strecker (Ann Chem Pharm 1868, 148, 77) demonstrated the presence of choline in bile. From all these investigations he proposed a structure for lecithin, including oleic acid, margaric acid, phosphoglyceric acid and choline (Gobley M., J Pharm Chim 1874, 19, 346).


The phospholipid chemistry made considerable progress with Thudichum (1828-1901). He isolated and characterized many phospholipid fractions using only their nitrogen/phosphorus ratio (Treatise on the chemical constitution of the brain“, Baillière, Tindall and Cox, London, 1884). He characterized “cephalin” (now phosphatidylethanolamine), distinct from lecithin by solubility properties. He isolated ethanolamine from the cephalin fraction but he considered it as a decomposition product of choline. Ethanolamine phospholipids were described later in the Institute of Physiology and Chemistry in Strasbourg, France (Baumann A., Biochem Z, 1913, 54, 30 and Renall M.H., Biochem Z 1913, 55, 296). Thudichum isolated also a phospholipid he named sphingomyelin (from greek sphingein, to bind tight – myelos, marrow) and described its molecular constituents. After alkaline hydrolysis, he successfully obtained its two constituents bases, sphingosine and choline, in addition  to phosphoric acid and a fatty acid. From his studies, Thudichum concluded that phospholipids are “the center, life, and chemical soul of all bioplasm“.


In 1927 three well-defined phospholipids had been described: lecithin, cephalin and sphingomyelin. Later, several others were added to that list: phosphatidic acid isolated from cabbage leaves in 1927 (Chibnall A.C., Biochem J 1927, 21, 233), one acetal phosphatide (now plasmalogen) isolated from beef heart in 1939 (Feulgen R.Z., Physiol Chem 1939, 260, 217). Folch made an important scientific contribution in isolating from brain phosphatidylethanolamine, phosphatidylserine and an inositol phospholipid as components of “cephalin” in 1942 and a “diphosphoinositide” in 1949 (Folch J., J Biol Chem 1949, 177, 497). Cardiolipin was also isolated from brain in 1944 (Pangborn M.C., J Biol Chem 1944, 153, 343) .


During a long time, separation of phospholipids was based on their solvent solubilities. In one of his most famous paper, Folch (J Biol Chem 1942, 146, 35) exploited this peculiarity to separate brain cephalin into three fractions containing ethanolamine, serine and inositol.

Advances in our knowledge of phospholipids have depended upon new methods of separation and analysis. In 1936, first appeared the use of a column of aluminum oxide (Thannhauser et al., J Biol Chem 1936, 116, 527), in 1956 the use of chromatography on silica-impregnated paper (Marinetti et al., Biochim Biophys Acta 1954, 14, 374),and around 1960 the use of thin-layer chromatography (Wagner H. et al., Biochem Z 1961, 334, 175).




No general agreement exists on the best way to classify phospholipids but most classifications contain a category for the glycerol-containing phospholipids (Glycerophosphatides, formerly Phosphoglycerides) and one for the sphingolipids (Sphingosyl phosphatides, formerly Phosphosphingolipids). More recently, new class of phospholipids have been described: N-acyl-O-phosphocholineserines found in human and animal tissues and alkylphosphocholines which were obtained by chemical synthesis.

1 – The term glycerophospholipid signifies any derivative of sn-glycero-3-phosphoric acid that contains at least one O-acyl, or O-alkyl or O-alk-1′-enyl residue attached to the glycerol moiety and a polar head made of a nitrogenous base, a glycerol, or an inositol unit.




2 – The term sphingosyl phosphatide refers to lipids containing phosphorus and a long-chain base. Those containing also a glycoside moiety are considered elsewhere.




 3 – N-acyl-O-phosphocholineserines have been described for the first time in 2019 in plasma of subjects suffering Niemann-Pick disease type C1 (Sidhu R et al., J Lipid Res 2019, 60, 1410). This new class of phospholipids was also shown to be present in plasma and brain of Nieman-Pick’s cat models. All molecular species of this phospholipid have fatty chain ranging from C14 to C24, the palmitoyl (C16) being the most abundant. All species could be used as biomarker for the Niemann-Pick disease.




4 – Phospholipid-like molecules have been synthesized, the alkylphosphocholines, which have remarkable biological and therapeutic activities. They are phosphocholine esters of aliphatic longchain alcohols differing in chain length, unsaturation and position of the cis-double bond. Hexadecylphosphocholine (miltefosine), described as a new drug in cancer therapy, has been synthesized in 1992  (Eibl H et al., Prog Exp Tumor Res 1992, 34, 1). Chemically, it is the phosphocholine ester of hexadecanol and has similar physical properties as lysolecithin. That compound has been also used in the treatment of both cutaneous and visceral leishmaniasis (LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-2017 Mar 15).






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