Phosphate anhydride

The favored formation of a nucleoside 3 -(alkyl phosphate) was observed on treating the diphenyl phosphate anhydride of uridine 2, 3 -cyclic phosphate with benzyl alcohol.273 In a somewhat related reaction, on treatment with dicyclohexylcarbodiimide in aqueous pyridine, adenosine 2 (3 )-phosphate gave, initially, the 2, 3 -cyclic phosphate, which, on further reaction with the diimide, gave a mixture of the N-phosphonourea nucleoside 44 and its 2 -isomer, in unequal amounts.269 This type of reaction does not seem to occur with... 

The pentose phosphates formed in the transketolase reactions—ribose 5-phosphate and xylulose 5-phos-phate—are converted to ribulose 5-phosphate (steps (7) and (3)), which in the final step ( ) of the cycle is phosphorylated to ribulose 1,5-bisphosphate by ribulose 5-phosphate kinase (Fig. 20-13). This is the third very exergonic reaction of the pathway, as the phosphate anhydride bond in ATP is swapped for a phosphate ester in ribulose 1,5-bisphosphate. 

The AG° values for the hydrolysis of any P - O - P bond of ATP, inorganic pyrophosphate, or any acyl CoA thiolester are all about -34 kj / mole, while the corresponding figure for the hydrolysis of a mixed carboxylic phosphate anhydride is about -55 kj / mole. Calculate the value of AG° for the following reaction describing the activation of fatty acids to the fatty acyl adenylate. 

Of particular importance is the conversion of much of the energy that results from photosynthesis, or from the oxidation of fats, carbohydrates, and proteins in cells into formation of phosphate ester bonds (C—O—P) or phosphate anhydride bonds (P—O—P). The energy so stored is used in other reactions, the net result of which is hydrolysis ... 

How do mitochondria couple such different types of reactions as electron transfer and the formation of a phosphate anhydride bond We explore this question in the following sections. 

The equilibrium constant for this reaction is about 1, so that the energy derived from the cleavage of the phosphate anhydride of ATP is conserved in the mixed anhydride. Aminoacyl-AMP remains tightly bound to the enzyme and, as we will soon show, this fact has allowed researchers to crystallize this important complex and analyze its structure. 

A perusal of current biochemistry texts suggests that the use of the squiggle has largely died out, but the concept of a group potential and the importance of these phosphate anhydride bonds in energy storage and transfer is universally accepted. Lipmann shared the Nobel Prize in Physiology/Medicine in 1953 with Hans Krebs of the Krebs (citric acid) cycle. His Nobel citation read in part,... 

A phosphate anhydride bond is hydrolyzed and a phosphate ester bond is formed with the C-3 of ribose. 

Phosphate anhydrides are the principle stores of biochemical energy. The phos-phoanhydride bond of polyP has a standard free energy of hydrolysis of approximately -9.7 kcal, within the range of that of other cellular phosphorylating agents such as ATP (-7.3 kcal) and phosphocreatine (-10.3 kcal).33 As a consequence of its intermediate position in the thermodynamic scale, polyPs can both transfer and accept phosphates from other phosphate anhydrides, and this is apparently the... 

GAPDH catalyzes the reversible oxidative phosphorylation of G-3P in a reaction that couples the oxidation of an aldehyde to the synthesis of a high energy phosphate anhydride, 1,3-diphospboglycerate (cf. 178), according to the equation... 

Leman LJ, Orgel LE, Ghadiri MR. Amino acid dependent formation of phosphate anhydrides in water mediated by carbonyl sulfide. J. Am. Chem. Soc. 2006 128 20-21. 

Biologically relevant vanadate esters (33-35) and a mixed vanadate-phosphate anhydride (36) Ad = adenosyl. For 33, the oxidation of activated glucose to gluconic acid (the lactone form is shown), as catalysed hy glucose-6-phosphate dehydrogenase (Glu-6PDH), is also depicted. 

An RNA aptamer has been selected to activate the carboxylic acid of amino acids that mimics the formation of a mixed phosphate anhydride synthesis of aminoacyl tRNA synthetases. The optimal aptamer requires only Ca + for the reaction, and operates at low pH with Xm 50 mM and /ccat 1.1 min for the activation of leucine. This lends support to the concept of translation in an RNA-based world. An RNA-cleaving DNAzyme has been used to target a chemokine receptor required by HIV-1 for entry into susceptible cells. The DNAzyme was found to be very efficient, and specifically interfered with the fusion of cells that harboured the T-lymphocytotropic HIV-1 envelope. 

The acyl-phosphate group at position 1 is much more energy rich than the phosphate anhydride of ATP, so 1,3BPG has the energy to drive synthesis of ATP from ADP + Pi, which it does in the glycolysis reaction catalyzed by the enzyme phosphoglycerate kinase. 

Because ATP can transfer a phosphate group, we say that ATP has a high "phosphoryl group transfer potential" rather than calling it a high energy compound. The phosphate anhydride bonds of ATP, ADP,... 

For the production of glycinamide ribonucleotide, an acyl phosphate (anhydride) intermediate is formed by reaction of ATP -with a carboxylic acid of an amino acid (glycine), whereas in the production of guanylate (GMP) a phosphoryl ester intermediate is formed by reaction of ATP with an enol alcohol on the purine ring of the nucleotide. 

Chapter 3 introduces ATP as a nucleoside triphosphate building block involved in RNA synthesis. The hydrolysis of the terminal phosphate anhydride bond when ATP is converted into adenosine diphosphate (ADP) releases energy. Further hydrolysis of ADP is possible, giving rise to adenosine monophosphate (AMP), with the release of a slightly smaller amount of energy. 

Many metabolites, especially those involved in glycolysis (Sec. 10.6) and the Krebs cycle (Sec. 10.7), have high-energy phosphate-ester bonds. Compared with these metabolites, ATP is an intermediate with respect to the amount of energy stored in its phosphate anhydride bonds. This makes sense, because a denomination of currency would not be practical if it needed to be changed (the energy content split up into smaller packets) each time it was used. 

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