Hydrolysis of ATP to AMP

FIGURE 24.7 The acyl-CoA synthetase reaction activates fatty acids for /3-oxidation. The reaction is driven by hydrolysis of ATP to AMP and pyrophosphate and by the subsequent hydrolysis of pyrophosphate. 

The carboxyl group of a fatty acid provides a point for chemical attack. The first step is a priming reaction in which the fatty acid is converted to a water-soluble acyl-CoA derivative in which the a hydrogens of the fatty acyl radicals are "activated" (step a, Fig. 17-1). This synthetic reaction is catalyzed by acyl-CoA synthetases (fatty acid CoA ligases). It is driven by the hydrolysis of ATP to AMP and two inorganic... 

The citrulline is then condensed with aspartate, the source of the second nitrogen atom in urea, by the enzyme argininosuccinate synthetase to form argininosuccinate. This reaction is driven by the hydrolysis of ATP to AMP and PP , with subsequent hydrolysis of the pyrophosphate. Thus both of the high-energy bonds in ATP are ultimately cleaved. 

Once citrulline is in the cytosol, argininosuccinic acid is formed by condensation of citrulline with aspartate. This is where the second nitrogen atom enters the cycle. Argininosuccinate synthetase, a homotetramer of a 46-kd polypeptide catalyzes the reversible reaction accompanied by hydrolysis of ATP to AMP and pyrophosphate. The subsequent hydrolysis of pyrophosphate shifts the equilibrium to the right and results in the consumption of two high-energy phosphate bonds. 

The activation of a fatty acid induces the formation of a thioester of fatty acid and CoA. The process is coupled to the hydrolysis of ATP to AMP. For palmitic acid, the reaction is ... 

ATP pyrophosphohydrolase catalyzes the hydrolysis of ATP to AMP and pyrophosphate (PPi). It is an activity that may be involved in several functions,... 

The A G° of this reaction is close to 0, because the free energy of hydrolysis of the ester bond of aminoacyl-tRNA is similar to that for the hydrolysis of ATP to AMP and PPj. As vv e have seen many times, the reaction is driven by the hydrolysis of pyrophosphate. The sum of these three reactions is highly exergonic ... 

Based on +11.80 kcal moP for hydrolysis to P207 plus AG° of dissociation of HPjO as quoted by Alberty, R. A. (1969) J.Biol.Chem. 244,3290-3324. However, 1.017 kcal moP was added to the value of 11.80 to make it consistent with that for hydrolysis of ATP to ADR Reevaluation by Frey and Arabshahi (1995) Biochemistry 34,11307-11310, indicates that AG (pH 7) for hydrolysis of ATP to AMP + PPj is 10 kJ mol more negative than is shown here. 

Citrulline combines with aspartate to form argininosuccinate in a reaction that is driven by the hydrolysis of ATP to AMP and inorganic pyrophosphate. 

The answer is c. (Murray, pp 452-467. Scriver, pp 3-45. Sack, pp 1—40. Wilson, pp 101—120.) Two molecules of GTP are used in the formation of each peptide bond on the ribosome. In the elongation cycle, binding of aminoacyl-tRNA delivered by EF-Tu to the A site requires hydrolysis of one GTE Peptide bond formation then occurs. Translocation of the nascent peptide chain on tRNA to the P site requires hydrolysis of a second GTE The activation of amino acids with aminoacyl-tRNA synthetase requires hydrolysis of ATP to AMP plus PP,. 

The first reaction in the fatty acid oxidation sequence is the thioesterification of the acid by CoA-SH. This involves bond formation between the CoA-S and the fatty acid and is therefore endergonic it is achieved by linking it to the simultaneous hydrolysis of ATP to AMP. The enzyme which does the job is a thiokinase (27). 

In the cytosol, free fatty acids are esterified to coenzyme A to form a fatty acyl CoA in an exergonlc reaction coupled to the hydrolysis of ATP to AMP and PPj (inorganic pyrophosphate) ... 

Mathematical Show that the hydrolysis of ATP to AMP and 2P releases the same amount of energy by either of the two following pathways. 

Now we discuss a deficiency of the Hopfield-Ninio scheme. Over a wide range of conditions, the turnover number for the hydrolysis of ATP to AMP catalyzed by IRS in the presence of valine and tRNA is identical to that for the isoleucylation of tRNA catalyzed by the enzyme when the valine is replaced by [ C]Ile. This is possible only when the diserimination through hydrolysis occurs after the rate-limiting step. To the contrary, the KPR scheme proposed by Hopfield considers that the discrimination step will be before the rate-limiting product formation step. 

When the hydrolysis of ATP to AMP occurs during metabolism, it is usually followed by the immediate hydrolysis of the pyrophosphate, which releases even more free energy ... 

We start with the activation of stearic acid by reacting it with coenzyme A to form stea-royl CoA. The energy needed to cause this reaction to occur comes from the hydrolysis of ATP to AMP and PP, and the subsequent hydrolysis of PP, to 2P,. This is equivalent to hydrolyzing two molecules of ATP to ADP. 

Guanine formation occurs following oxidation in position 2, to form xanthylic acid." This oxidation has been demonstrated with a DPN-requiring enzyme from bone marrow. Subsequent animation occurs through different mechanisms in animal and bacterial systems. In bone marrow extracts the amide of glutamine is transferred, while in bacterial extracts ammonia is utilized more readily than glutamine. The utilization of ammonia by the bacterial system is accompanied by the hydrolysis of ATP to AMP and PP. In addition to these reactions, it is known that adenine and guanine can be interconverted, but the enzymatic mechanisms are not known. 

In a number of cases, there is a further mechanism to ensure that the equilibrium of an ATP-linked reaction is kept well to the right, to such an extent that the reaction is essentially irreversible. The reaction shown in Figure 3.6 results in the hydrolysis of ATP to AMP and pyrophosphate. There is an active pyrophosphatase in cells, which catalyses the hydrolysis of pyrophosphate to yield 2 mol of phosphate, so removing one of the products of the reaction, and ensuring that it is essentially irreversible. 

RNA ligases catalyze the 3 —> 5 phosphodiester bond formation of RNA molecules with concomitant hydrolysis of ATP to AMP and PP . Initially detected as an activity that catalyzes the circularization of polyribonucleotides with 3 -OH and 5 -P ends (1), the RNA ligase is found in E. coli after infection by T-even (but not T-odd) bacteriophages. The enzyme can carry out intermolecular as well as intramolecular ligation reactions on ssRNA, ssDNA, or a variety of oligonucleotides and polynucleotides having 5 -P and 3 -OH termini. 

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