Pyrophosphate bond

Ligases (syniheiases). Enzymes catalysing the joining together of two molecules coupled with the hydrolysis of a pyrophosphate bond in ADP or a similar triphosphate. They include some carboxylases and many enzymes known as synthetases. 

Ligases (synthetases) - catalyzing the condensation of 2 molecules coupled with the cleavage of a pyrophosphate bond of ATP or similar triphosphate. 

C. Reactions.—The iV-chloroquinonimine (50) reacts with monoalkyl phosphates in dry pyridine to give symmetrical pyrophosphate esters. If present in excess it can react further, giving an intermediate which is attacked by alcohols or water with cleavage of the pyrophosphate bond. 

Such enzymes catalyse the condensation of specific compounds, accompanied by the breakdown of a pyrophosphate bond in adenosine triphosphate (10.64). Adenosine is the condensation product of a pentose (D-ribofuranose) and a purine (adenine). Scheme 10.15 shows the action of glutamine synthetase on a mixture of L-glutamic acid (10.65) and... 

Isotope exchange experiments with purified F reveal a remarkable fact about the enzyme s catalytic mechanism on the enzyme surface, the reaction ADP + P, ATP + H20 is readily reversible—the free-energy change for ATP synthesis is close to zero When ATP is hydrolyzed by Fi in the presence of 180-labeled water, the Pj released contains an 180 atom. Careful measurement of the 180 content of P, formed in vitro by Fx-catalyzed hydrolysis of ATP reveals that the P, has not one, but three or four 180 atoms (Fig. 19-21). This indicates that the terminal pyrophosphate bond in ATP is cleaved and re-formed repeatedly before P, leaves the enzyme surface. With P, free to tumble in its binding site, each hydrolysis inserts 180 randomly at one of the... 

Ligases—The synthetic joining of two molecules, coupled with the breakdown of a pyrophosphate bond in a nucleoside triphosphate. 

In this equation, Starch"+1 represents the starch molecule after addition of a glucosyl residue. The reactions in this conversion, which include cleavage of both of the pyrophosphate bonds of ATP and the formation of a new pyrophosphate bond, are a bit more complex than in the case of a simple kinase reaction, but the thermodynamic effect is merely that of adding an ATP-to-ADP conversion in the direction of polysaccharide synthesis. Thus, the pseudocycle that connects glucose-1 -phosphate and starch is energetically equivalent to any other in which two oppositely directed conversions differ by one ATP-to-ADP conversion. 

Specific nucleotide recognition in the ternary complex between the enzyme lactate dehydrogenase and the modified coenzyme NAD+-pyruvate (NAD = nicotinamide-adenine-dinucleotide). NAD+ consists of two nucleotides, adenosine-5 -phosphate and nicotinamide ribose-5 -phosphate, which are linked through a pyrophosphate bond. 

Because of coupling (see Chapter 7) there are relationships between the thermodynamic properties of reactions in some of the EC classes. All oxidoreductase reactions can be considered to be coupled reactions because each one can be divided into two, or in a some cases, three half reactions that do not share atoms but are connected by formal electrons. Transferase reactions can each be considered to result from the coupling of two oxidoreductase reactions or two hydrolase reactions. Fifteen examples are discussed in reference (6). Each of the coupled reactions contributes its A, G ° and A, A h to the coupled reaction. Hydrolase reactions and isomerase reactions are never coupled reactions. Some lyase reactions are coupled. Ligase reactions are all coupled by definition because they join together two reactions with the hydrolysis of a pyrophosphate bond in ATP or a similar triphosphate. A spectacular example of coupling is provided by EC 6.3.5.4 because there are seven reactants. This never happens in chemistry. 

Synthase—a lyase that catalyzes a synthesis that does not include breaking a pyrophosphate bond. Example ... 

Extra p s can be added to indicate pyrophosphate bonds, e.g. pppGp guanosine tetraphosphate. 

ATP adenosine triphosphate, a biological energy-transfer molecule containing high-energy pyrophosphate bonds. 

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