Energy-Rich Phosphate Esters

Concomitantly with these discoveries, a closer understanding of the pattern of reactions of anaerobic glycolysis elucidated the exact enzymatic steps which are interlocked with the formation of ATP. Taken together, this nexus of discoveries concerning the generation of ATP in the fermentation of glucose and its utilization in the performance of muscular work must be regarded as one of the fundamental achievements of biochemistry to date. 

In a paper which has already begun to assume the status of a classic, Lipmann in 1941 did much to make clear the chemical relationships under- 

ATP FAD, DPN, TPN Thiamine pyrophosphate Inorganic pyrophosphate II. Low-Energy Phosphate Esters 

Phosphate esters of alcohols Glycerophosphate Hexose phosphates Phosphorylcholine 

The striking difference between the free energy of hydrolysis of these two groups of compounds has naturally been the object of much speculation from the purely physicochemical point of view. Attempts have been made by Kalckar, Oesper, and Hill and Morales to account for the magnitude of the free energy change noted upon the hydrolysis of energy-rich phosphate esters. 

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Phytic acid (D 1.3) Energy rich phosphate ester, used in ATP formation in plants... 

Phosphate esters are usually synthesized by means of phosphoiylating transferases called kinases, which catalyze the transfer of a phosphate moiety (or a di- ° or triphosphate moiety) from an energy-rich phosphate donor, such as ATP. Due to the high price of these phosphate donors, they cannot be employed in stoichiometric amounts. Since ATP cannot be replaced by less expensive man-made chemical equivalents, efficient in-situ regeneration (i.e., recycling) is necessary in order to reduce the cost of enzymatic phosphorylations. Fortunately, ATP recycling has become feasible on a molar scale [520, 521]. On the other hand, reversal of phosphate ester hydrolysis, i.e., the equivalent condensation reaction, has been performed in solvent systems with a reduced water content. Such systems would eliminate the use of expensive or chemically labile phosphate-donors but it is questionable if they will be of general use [522]. 

An example of the transformation of an ordinary phosphate ester into an energy-rich phosphate is provided by another reaction of the glycolysis chain the conversion of 2-phosphoglyceric add into phosphoenolpyruvic add followed by a transphosphorylation. The reaction (a dehydration), catalysed by enolase, results in the redistribution of the internal energy of the molecule with concentration of around 16,000 calories in the enol-phosphate bond. 

The thioester hypothesis can be summed up as follows the formation of thiols was possible, for example, in volcanic environments (either above ground or submarine). Carboxylic acids and their derivatives were either formed in abiotic syntheses or arrived on Earth from outer space. The carboxylic acids reacted under favourable conditions with thiols (i.e., Fe redox processes due to the sun s influence, at optimal temperatures and pH values) to give energy-rich thioesters, from which polymers were formed these in turn (in part) formed membranes. Some of the thioesters then reacted with inorganic phosphate (Pi) to give diphosphate (PPi). Transphosphorylations led to various phosphate esters. AMP and other nucleoside monophosphates reacted with diphosphate to give the nucleoside triphosphates, and thus the RNA world (de Duve, 1998). In contrast to Gilbert s RNA world, the de Duve model represents an RNA world which was either supported by the thioester world, or even only made possible by it. 

When two phosphate residues bond, they do not form an ester, but an energy-rich phosphoric acid anhydride bond, as... 

In 1951, Feodor Lynen (1911-1979) and his coworker E. Reichert demon-started that S-acetyl coenzyme A is a more generally implicated form of active acetate than acetyl phosphate that was recognized in this role by Fritz Lipmann in 1940. The thiol ester character of 5-acetyl Co A called the attention of Th. Wieland to energy-rich S-acyl compounds as promising intermediates for the formation of the peptide bond. In 1951, the same year when the isolation of 5-acetyl CoA was published [3], Wieland and his coworkers described [4] the preparation of thiophenyl esters of benzyloxycarbonyl-amino acids and benzyloxycarbonyl-peptides and their application in the synthesis of blocked peptides ... 

High energy bonds, energy-rich bonds chemical bonds which release more than 25 kJ/mol on hydrolysis. They are usually esters (enol, thio and phosphate esters), acid anhydrides, or amidine phosphates. 

The purine glycosides adenine and guanine are constituents of the nucleic acids of all living beings. Their phosphate esters play an important role in metabolism as energy-rich compounds (C 1.1). 

The significance of phosphate esters and of the difference between energy-rich and energy-poor phosphate compounds was spelled out in a beautiful classical review by Fritz Lipmann in the first volume of Advances in Enzymology in 1941. The squiggle ( ) was bom in this article. 

Substrate-level phosphorylation can be either aerobic or anaerobic. During oxidation by electron loss, an ester-phosphoric bond is formed. It is an energy-rich bond between the oxidized carbon of the substrate and a molecule of inorganic phosphate. This bond is then transferred to the ADP by transphosphorylation, thus forming ATP. This process takes place during glycolysis. 

Phosphate is again present in an energy-rich form (namely the enol ester). It can be transferred by phosphopyruvate kinase to ADP this transfer affords pyruvic acid, which is the most important metabolite of both anaerobic and aerobic carbohydrate metabolism. 

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