1,3-Diphosphoglyceric acid synthesis

Kulaev (1979) showed that such evolutionary conserved organisms as Micrococcus lysodeicticus and P. shermanii possess a glycolysis-dependent polyphosphate synthesis system in addition to the ATP-dependent one. It has been established (Bobic, 1971 Kulaev et al, 1973) that the biosynthesis of polyphosphates in propionibacteria can proceed both via the terminal phosphate of ATP as well as that of 1,3-diphosphoglyceric acid (1,3-DPGA) ... 

The major source of the high energy phosphate found in all of the nucleoside polyphosphates is ATP, and its synthesis can be largely accounted for by oxidative phosphoiylation and by the transfer of phosphate from 1,3-diphosphoglyceric acid and phosphoenolpyruvate to adenosine diphosphate (ADP). However free ribo- and deoxyribonucleoside polyphosphates of the purine and pyrimidine series are found in tissues 98-102). The means by which nucleoside polyphosphates other than those of the adenosine series acquire their phosphate will now be discussed. 

In view of the known binding capacity of deoxygenated hemoglobin for 2,3-diphosphoglyceric acid (2,3-DPG) and adenine nucleoti-des it appeared likely that the inhibitory action of these effectors and accordingly the Pi requirement for the synthesis of PRPP in RBC would be considerably diminished under anaerobic conditions. This prediction was borne out by the data presented in Fig. 

The concentration of PRPP in erythrocytes was measured using the procedure of Sperling et al (5) in which phosphoribosyl-transferase activity present in the haemolysate is utilized. PRPP synthesis during the assay was inhibited by 2,3-diphosphoglyceric acid. Since some of the heterozygotes studied had low HGPRTase activity, PRPP was assayed using the haemolysate adenine phospho-ribosyltransferase activity with radioactive adenine as the second substrate. 

This is another exampie of substrate-level phosphorylation, but differs from the earlier example that involved hydrolysis of a mixed anhydride. Here, we have merely the hydrolysis of an ester, and thus a much lower release of energy. In fact, with 1,3-diphosphoglycerate, we specifically noted the difference in reactivity between the anhydride and ester groups. So how can this reaction lead to ATP synthesis The answer lies in the stability of the hydrolysis product, enolpyruvic acid. Once formed, this enol is rapidly isomerized to its keto tautomer, pyruvic acid, with the equilibrium heavily favouring the keto tautomer (see Section 10.1). The driving force for the substrate-level phosphorylation reaction is actually the position of equilibrium in the subsequent tautomerization. 

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