Phosphatides and Phosphagens
The important phosphorus compounds in organisms are much more complex than the simple salts, to which Nietzsche attributed such influence on man’s character. Long before he wrote, it was known that phosphoric acid combines not only with inorganic bases to form salts, but with alcohols to form esters. In the middle of the 19th century, Théophile Juste Pelouze (1807-1867) extended this knowledge to an ester of glycerol. This proved to be significant in several respects. Glycerol had been shown by Michel Chevreul (1786-1889) as the substance in fats that is released in the process of soap boiling, when the fatty acids are converted into their salts. That it has the nature of an alcohol had been demonstrated by Marcellin Berthelot. Instead of one “alcoholic” hydroxyl group, OH, like ethanol (the alcohol of fermentation), or two hydroxyl groups (like ethylene glycol), glycerol contains three such groups. It was the only “natural” alcohol known at that time. That this alcohol would combine with phosphoric acid could be predicted, but that the ester, as obtained by Pelouze, still contained free acidic functions and formed a water-soluble barium salt was a new experience.
Shortly after this experience had been gained, it became valuable for understanding the chemical nature of a new substance extracted from a natural organ. This substance was named lecithin by its discoverer, Nicolas Théodore Gobley27 (1811-1876), because he obtained it from egg yolk (in Greek, lékidos). He used ether and alcohol for this extraction. Had he used water and mineral acid instead, he would not have found lecithin, but only its components. As Gobley and, slightly later, Oscar Liebreich (1839-1908), subjected lecithin to treatment with boiling water and acid, they separated it into three parts. One of them was the glycerophosphoric acid of Pelouze, the second was the well-known stearic acid of Chevreul, but the third was somewhat mysterious. This third substance was the same as one previously noticed when nerves had been subjected to an extraction by boiling water and acid and, therefore, called nerve-substance or neurine. Adolf Friedrich Strecker (1822-1871) established the identity of this neurine with a product he had extracted from bile and which went under the name of choline. Adolphe Wurtz (1817-1884) succeeded in synthesizing this substance from ethylene oxide, CH2.O.CH2 and trimethylamine N(CH3)3.28 Thus, all three parts were identified, and Strecker put them together to construct a chemical formula for lecithin, glycerophosphoric acid combined with a fatty acid and with choline (a hydrate of neurine).
| { | OH | } | ||
| N | (CH3)3 | Choline | ||
| C2H4O |
| C18H33O2 | } | HO | } | ||
| PO | |||||
| C16H31O2 | C3H5O | ||||
| Fatty Acids | Glycerophosphate | ||||
| ‘—————v————’ | |||||
| Lecithin | |||||
| according to Strecker | |||||
This formula was not quite correct. Richard Willstätter showed that an internal neutralization takes place between the amino group and the free acidic residue. This is expressed in his lecithin formula of 1918.
When the aim was to distill elementary phosphorus out of an organic material, it did not matter whether this was fresh or putrified. For obtaining lecithin out of egg yolk and similar materials, it was essential to use it in fresh condition. Otherwise, enzymes would have decomposed it. Through more recent work, four enzymes have been separated, which act specifically in decomposing lecithin. Enzyme A removes one fatty acid and leaves a complex residue, called lysolecithin, intact. Enzyme B attacks this residue and splits off the remaining fatty acid group from it, enzyme C liberates only the choline from lecithin, and enzyme D opens lecithin at the ester bond between glycerol and phosphoric acid. This is shown in the following diagram.
| Enzymatic Splitting of Lecithins | ||
|---|---|---|
| Enzyme | Substrate | Products |
| A | Lecithin | Lysolecithin and fatty acids. |
| B | Lysolecithin | Glycero-phospho-choline and fatty acids. |
| C | Lecithin | Phosphatidic acid and choline. |
| D | Lecithin | Phosphoryl choline and diglyceride. |
Several fatty acids can be present in lecithin from various sources: palmitic and oleic acid, besides the stearic acid which at first had been thought the only one involved. In another group of extracts from brain or nerve tissue, amino-ethanol H2NCH2CH2OH is found instead of the choline of lecithin. The variations include the alcohol, to which the fatty acids and choline phosphate are attached, for example, glycerol can be replaced by the so-called meat-sugar, inositol, which has six hydroxyl groups in its hexagon-shaped molecule C6H6(OH)6.
The generally similar behavior of these phosphate-and fat-containing substances was emphasized by Ludwig Thudichum (1829-1901). He coined the name phosphatides for this group of substances from seeds and nerves.29 His work on the phosphates in brain substance aroused particular interest. When William Crookes drew his highly imaginative picture of an “evolution” of the chemical elements, he put into it “phosphorus for the brain, salt for the sea, clay for the solid earth....”30 But phosphatides occur in many places of organisms, in bacteria, in leaves and roots of plants, in fat and tissues of animals. And where phosphatides are found, there are also enzymes that specifically act on them. They are called phosphatases to imply that they split the phosphatides. In addition, enzymes are present, which transfer phosphate groups from one compound to another. They are more abundant in seeds of high fat content than in the more starch-containing seeds, but even potatoes and orange juice have phosphatases.31
Thus, from phosphatides, phosphoric acid is generated, and they could also be called phosphagens. Since 1926, however, the name phosphagens has been reserved for a group of organic substances that release their phosphoric acid very readily. The link between phosphorus and carbon is provided by oxygen in the phosphatides, by nitrogen in the phosphagens. In vertebrates, the basis for the phosphoric acid is creatine, whereas invertebrates have arginine instead.