Other high energy nucleotides

Other High-Energy Nucleotides Adenylate Energy Charge Major Metabolic Control Mechanisms Control of Enzyme Levels Control of Enzyme Activity (Figure 12.10)... 

Begirming and ending with ornithine, the reactions of the cycle consumes 3 equivalents of ATP and a total of 4 high-energy nucleotide phosphates. Urea is the only new compound generated by the cycle all other intermediates and reactants are recycled. 

Hydrolases represent a significant class of therapeutic enzymes [Enzyme Commission (EC) 3.1—3.11] (14) (Table 1). Another group of enzymes with pharmacological uses has budt-ia cofactors, eg, in the form of pyridoxal phosphate, flavin nucleotides, or zinc (15). The synthases, and other multisubstrate enzymes that require high energy phosphates, are seldom available for use as dmgs because the required co-substrates are either absent from the extracellular space or are present ia prohibitively low coaceatratioas. 

ATP is the primary high-energy phosphate compound produced by catabolism, in the processes of glycolysis, oxidative phosphorylation, and, in photosynthetic cells, photophosphorylation. Several enzymes then cany phosphoryl groups from ATP to the other nucleotides. Nucleoside diphosphate kinase, found in all cells, catalyzes the reaction... 

The purine bases are produced de novo by pathways that use amino acids as precursors and produce nucleotides. Most de novo synthesis occurs in the hver (Fig. 41.2), and the nitrogenous bases and nucleosides are then transported to other tissues by red blood cells. The brain also synthesizes significant amounts of nucleotides. Because the de novo pathway requires six high-energy bonds per purine produced, a salvage pathway, which is used by many cell types, can convert free bases and nucleosides to nucleotides. 

The cyclic product is extremely sensitive to moisture (hydrolysis) and was more readily isolated as the cyclic diester. An interesting correlation has been observed the phenyl triesters of high energy cyclic phosphates (cyclic nucleotides, ethylene phosphate) are very reactive species, susceptible to decomposition. On the other hand, the phenyl triesters of low energy cyclic phosphates are stable, crystalline compounds. Hence, for example, the phenyl triester of trimethylene phosphoric acid is a crystalline compound readily prepared in high yield by reaction of 1,3-propanediol with phenyl phosphorodichloridate. 

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