Acid anhydride bond

Hydrolases catalyze the hydrolytic cleavage of C—C, C—O, C—N, P—O, and certain other bonds, including acid anhydride bonds. 

A primed numeral locates the position of the phosphate on the sugars of mononucleotides (eg, 3 -GMP, 5 -dCMP). Additional phosphoryi groups linked to the first by acid anhydride bonds form nucleoside diphosphates and triphosphates. 

Nucleotides are formed when one or more phosphate groups is attached to the 5 carbon of a nucleoside (Figure 1-1-6). Nucleoside di- and triphosphates are high-energy compounds because of the hydrolytic energy associated with the acid anhydride bonds (Figure 1-1-7). 

Compounds of one acid with another are referred to as acid anhydrides. A particularly large amount of energy is required for the formation of an acid—anhydride bond. Phosphoric anhydride bonds therefore play a central role in the storage and release of chemical energy in the cell (see p. 122). Mixed anhydrides between carboxylic acids and phosphoric acid are also very important energy-rich metabolites in cellular metabolism. 

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

Phosphoric acid molecules can form acid-anhydride bonds with each other. It is therefore possible for two nucleotides to be linked via the phosphate residues. This gives rise to dinucleotides with a phosphoric acid-anhydride structure. This group includes the coenzymes NAD(P) " and CoA, as well as the flavin derivative FAD (1 see p. 104). 

Acyl residues are usually activated by transfer to coenzyme A (2). In coenzyme A (see p. 12), pantetheine is linked to 3 -phos-pho-ADP by a phosphoric acid anhydride bond. Pantetheine consists of three components connected by amide bonds—pantoic acid, alanine, and cysteamine. The latter two components are biogenic amines formed by the decarboxylation of aspartate and cysteine, respectively. The compound formed from pantoic acid and p-alanine (pantothenic acid) has vitamin-like characteristics for humans (see p. 368). Reactions between the thiol group of the cysteamine residue and carboxylic acids give rise to thioesters, such as acetyl CoA. This reaction is strongly endergonic, and it is therefore coupled to exergonic processes. Thioesters represent the activated form of carboxylic adds, because acyl residues of this type have a high chemical potential and are easily transferred to other molecules. This property is often exploited in metabolism. 

In standard conditions, the change in free enthalpy AG° (see p. 18) that occurs in the hydrolysis of phosphoric acid anhydride bonds amounts to -30 to -35 kj mol at pH 7. The particular anhydride bond of ATP that is cleaved only has a minor influence on AG° (1-2). Even the hydrolysis of diphosphate (also known as pyrophosphate 4) still yields more than -30 kJ mol . By contrast, cleavage of the ester bond between ribose and phosphate only provides -9 kJ mol (3). 

The subsequent cleavage of the thio-ester succinylCoA into succinate and coenzyme A by succinic acid-CoA ligase (succinyl CoA synthetase, succinic thiokinase) is strongly exergonic and is used to synthesize a phosphoric acid anhydride bond ( substrate level phosphorylation , see p. 124). However, it is not ATP that is produced here as is otherwise usually the case, but instead guanosine triphosphate (CTP). However, GTP can be converted into ATP by a nucleoside diphosphate kinase (not shown). 

Energy requirements in protein synthesis are high. Four energy-rich phosphoric acid anhydride bonds are hydrolyzed for each amino acid residue. Amino acid activation uses up two energy-rich bonds per amino acid (ATP AMP + PP see p. 248), and two GTPs are consumed per elongation cycle. In addition, initiation and termination each require one GTP per chain. 

Look at ATP. In the figure the bolded region is the "recognition" part of the molecule, while the polyphosphate is the chemically active portion. Each of the phosphoric acid anhydride bonds is unstable. That is hydrolyzing either will release a lot of energy. 

Coenzymes have many functions. They carry chemical energy in their easily hydrolyzed acid-anhydride bond, for instance, ATP. ATP is one of the most important coenzymes as shown in Fig. 7.1. 

As noted in the introduction, the effects of multiple modes of catalysis are often multiplicative rather than simply additive. Consequently, it is not surprising that a number of hydrolytic metalloenzymes have evolved that utilize a constellation of three metal ions in catalysis. Perhaps not coincidentally, all well-characterized examples of this class catalyze the hydrolytic cleavage of phosphate ester or phosphoric acid anhydride bonds, which represent a difficult and long-standing chemical problem. In every case but one, the metal ions in the trimetal centers are all zinc. As we shall see, alkaline phosphatase utilizes a Zn2Mg trinuclear center. It should be pointed out that in the older literature many of the enzymes discussed in this section have been described as containing dinuclear metal centers. Only in the last few years has it become clear that three metal ions are present and participate in catalysis by these systems. 

By copolymerising methacryloyl chloride and methacrylic acid with methyl methacrylate, it is possible to form intermolecular crosslinks (acid anhydride bonds) in situ on the appropriate substrate by heating the resist after spin coating (Figure 6.18). 

---