Phosphates in Biological Processes
The first indication that phosphorus is important for life came from the experience that plants take it up from the substances in the soil. They incorporate it in their body substance. What makes phosphorus so important that they cannot grow without it? The next insight was that animals acquire it from their plant food. It is then found in bones, in fat and nerve tissue, in all cells and particularly in the cell nuclei. What are its functions there?
The answers to such questions were developed from the study of a long-known process, the conversion of carbohydrates into carbon dioxide and alcohol by yeast. It started with Eduard Buchner’s discovery of 1890, that fermentation is produced by a preparation from yeast in which all living cells have been removed. When yeast is dead-ground and pressed out, the juice still has the ability to produce fermentation.
It is strange, but in many ways characteristic for the process of science, that the “riddle” of phosphorus in life was solved by first eliminating life. In such “lifeless” fermentations, Arthur Harden found that the conversion of sugar begins with the formation of a hexose phosphate (1904). The “ferment” of yeast, called zymase, proved to be a composite of several enzymes. Hans von Euler-Chelpin isolated one part of zymase, which remains active even after heating its solution to the boiling point. From 1 kilogram of yeast, he obtained 20 milligrams of this heat-stable enzyme, which he called cozymase and identified as a nucleotide composed of a purine, a sugar, and phosphoric acid.36 In the years between the two World Wars, zymase was further resolved into more enzymes, one of them the coenzyme I, which was shown to be ADP connected with another molecule of ribose attached to the amide of nicotinic acid, or diphosphopyridine nucleotide:
Its function is connected with the transfer of hydrogen between intermediates formed through phosphate-transferring enzymes. Fermentation proceeds by a cascade of processes, in which phosphate groups swing back and forth, and equilibria between ATP with ADP play a major role.
Many of the enzymes are closely related to vitamins. Thus, cocarboxylase A, which takes part in the separation of carbon dioxide from an intermediate fermentation product, is the phosphate of vitamin B1. Others of the B vitamins contain phosphate groups, for example those of the B2 and B6 group, and in B12, one lonely phosphate forms a bridge in the large molecule that contains one atom of cobalt: C63H90N14O14PCo. The formation of vitamin A from carotine occurs under the influence of ATP.
The first stages in fermentation are like those in respiration, which ends with carbon dioxide and water. These two are the materials for the reverse process in photosynthesis. When light is absorbed by the chlorophyll of green plants, one of the initial reactions is a transfer of hydrogen from water to a triphosphopyridine nucleotide, which later acts to reduce the carbon dioxide. Under the influence of ATP, phosphoglyceric acid is synthesized and further built up by way of carbohydrate phosphates to hexose sugars and finally to starch. In many starchy fruits, a small proportion of phosphate remains attached to the end product.
The synthesis of proteins is under the control of deoxyribonucleic acid or ribonucleic acid, abbreviated by the symbols DNA and RNA. The genes in the nucleus are parts of a giant DNA molecule. RNA is a universal constituent of all living cells. Where protein synthesis is intense, the content in RNA is high. Thus, the spinning glands of silkworms are extraordinarily rich in RNA.37
In his research on the radioactive isotope P32, George de Hevesy gained some insight into the surprising mobility of phosphates in organisms: “A phosphate radical taken up with the food may first participate in the phosphorylation of glucose in the intestinal mucose, soon afterwards pass into the circulation as free phosphate, enter a red corpuscle, become incorporated with an adenosine triphosphoric-acid molecule, participate in a glycolytic process going on in the corpuscle, return to circulation, penetrate into the liver cells, participate in the formation of a phosphatide molecule, after a short interval enter the circulation in this form, penetrate into the spleen, and leave this organ after some time as a constituent of a lymphocyte. We may meet the phosphate radical again as a constituent of the plasma, from which it may find its way into the skeleton.”38 Much has been added in the last 30 years to complete this picture in many details and to extend it to other biochemical processes, including even the changes of the pigments in the retina in the visual process, or in the conversion of chemical energy to light by bacteria and insects.