Phosphoanhydride bonds

An enzymatic reaction intermediate formed by phospho-ryl transfer to a carboxyl group on an enzyme. Acyl-phosphates are structurally analogous to acid anhydrides (R—CO —O —CO—R ), and they are thermodynamically less stable than either of the two phosphoanhydride bonds in ATP. This is evident by the fact that the acetate kinase reaction (ADP + acetyl-phosphate = ATP + acetate) favors ATP formation with an equilibrium constant of about 3,000. Acetyl-phosphate can be chemically synthesized by reacting orthophosphate with acetic anhydride. 

Hydrolysis of the terminal (or, /3-y) phosphoanhydride bond of ATP is the primary thermodynamic driving force in metabolism. Written as a biochemical equation at a specified pH, ATP hydrolysis can be represented as ... 

Inorganic pyrophosphatase [EC 3.6.1.1] plays a central role in phosphorus metabolism by catalyzing the hydrolysis of the phosphoanhydride bond of inorganic pyrophosphate (or, diphosphate PPi). This cleavage reaction acts in conjunction with pyrophosphate-forming ligases to provide an additional thermodynamic impetus for certain biosynthetic reactions. For example ... 

ATP is an energy rich molecule because its triphosphate unit contains two phosphoanhydride bonds. A large amount of free energy is liberated when ATP is hydrolysed to ADP or AMP. 

RGURE 8-40 The phosphate ester and phosphoanhydride bonds of ATP. Hydrolysis of an anhydride bond yields more energy than hydrolysis of the ester. A carboxylic acid anhydride and carboxylic acid ester are shown for comparison. 

Although the hydrolysis of ATP is highly exeigonic (AG ° = -30.5 kJ/mol), the molecule is kinetically stable at pH 7 because the activation energy for ATP hydrolysis is relatively high. Rapid cleavage of the phosphoanhydride bonds occurs only when catalyzed by an enzyme. 

FIGURE 13-11 Nucleoside triphosphates in RNA synthesis With each nucleoside monophosphate added to the growing chain, one PPi is released and hydrolyzed to two P,. The hydrolysis of two phosphoanhydride bonds for each nucleotide added provides the energy for forming the bonds in the RNA polymer and for assembling a specific sequence of nucleotides... 

Inorganic polyphosphate (polyP) is a linear polymer composed of many tens or hundreds of Pi residues linked through phosphoanhydride bonds. This polymer, present in all organisms, may accumulate to high levels in some cells. In yeast, for example, the amount of polyP that accumulates in the vacuoles would represent, if distributed uniformly throughout the cell, a concentration of 200 him (Compare this with the concentrations of other phosphoryl donors listed in Table 13-5.)... 

Nicotinamide adenine dinucleotide (NAD+ in its oxidized form) and its close analog nicotinamide adenine dinucleotide phosphate (NADP+) are composed of two nucleotides joined through their phosphate groups by a phosphoanhydride bond (Fig. 13-15a). Because the nicotinamide ring resembles pyridine, these compounds are sometimes called pyridine nucleotides. The vitamin niacin is the source of the nicotinamide moiety in nicotinamide nucleotides. 

Conversion of Succinyl-CoA to Succinate Succinyl-CoA, like acetyl-CoA, has a thioester bond with a strongly negative standard free energy of hydrolysis (AG ° = -36 kJ/mol). In the next step of the citric acid cycle, energy released in the breakage of this bond is used to drive the synthesis of a phosphoanhydride bond in either GTP or ATP, with a net AG ° of only -2.9 kJ/mol. Succinate is formed in the process ... 

The released energy of almost all the metabolic pathways is converted to the chemical energy of phosphoanhydride bonds in ATP. Cells use the energy released during hydrolysis of the ATP bonds to power energetically unfavorable processes. 

More than one hundred years ago, L. Liberman (1890) found high-polymeric inorganic polyphosphates (PolyPs) in yeast. These compounds are linear polymers containing a few to several hundred residues of orthophosphate (Pi) linked by energy-rich phosphoanhydride bonds. 

Inorganic polyphosphates (polyPs), also called condensed phosphates, are linear polymers of tetrahedral orthophosphate units linked through common oxygen atoms by phosphoanhydride bonds (Figure 1A). PolyPs can be formed in the laboratory or in nature by temperature- or pressure-induced condensation of acid orthophosphate salts accordingly, they are prepared synthetically by heating the... 

In reaction (1), which is catalyzed by a phosphohydrolase, or as it is more commonly called, an ATPase, the jS/y-phosphoanhydride bond of the ATP is cleaved, with the result that ADP and inorganic phosphate (Pj) are formed. Reaction (2), catalyzed by a pyrophosphohydrolase, cleaves the a,f.3 bond of the ATP, with the result that AMP and pyrophosphate (PR) are formed. Finally, (3) is the well-known reaction catalyzed by adenylate kinase, or myoki-nase, where ATP and AMP react to form two ADP molecules. Since reaction... 

ATP is a nucleotide consisting of an adenine, a ribose, and a triphosphate unit (Figure 14.3). The active form of ATP is usually a complex of ATP with Mg2+ or Mn2+ (Section 9.4.2). In considering the role of ATP as an energy carrier, we can focus on its triphosphate moiety. ATP is an energy-rich molecule because its triphosphate unit contains two phosphoanhydride bonds. A large amount of free energy is liberated when ATP is hydrolyzed to adenosine diphosphate (ADP) and orthophosphate (Pj) or when ATP is hydrolyzed to adenosine monophosphate (AMP) and pyrophosphate... 

The equilibrium constant for this reaction is close to 1, inasmuch as the number of phosphoanhydride bonds is the same on each side of the equation. Using the equation for the equilibrium constant for this reaction, show why changes in [AMP] are a more effective indicator of the adenylate pool than [ATP]. 

Note that two ATP equivalents are required the phosphoanhydride and thioester bonds are of similar free energies, so a second phosphoanhydride bond is also hydrolyzed to drive the reaction to completion. 

Structural formula of adenosine triphosphate (ATP) at pH 7.0, The three phosphate groups are identified by Greek letters a, fi, and y. The y- and S-phosphate groups are linked through phosphoanhydride bonds and their hydrolysis yields a large negative AG°, whereas the cr-phosphate linked by a phosphate ester bond has a much lower negative AG°. ... 

Although 52.6 kcal of free energy is available from the reaction, only 21.9 kcal is conserved in the formation of phosphoanhydride bonds at ATP. Formation of each phosphoanhydride bond requires 7.3 kcal (30.5 kJ), and 21.9 kcal accounts for three ATPs synthesized. The remainder of the energy is assumed to be dissipated as heat. 

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