Purine ribonucleotide interconversion function

As mentioned in Chapter 7, adenylosuccinate lyase not only functions in purine ribonucleotide interconversion, but also converts phosphori-bosyl aminoimidazole succinocarboxamide to phosphoribosyl amino-imidazole carboxamide. Kinetic studies show that these compounds are alternative substrates and products, respectively, with adenylosuccinate and adenylate, and attempts physically to separate the two activities have consistently failed. Genetic studies have shown that both activities are governed by the same locus and that mutant enzymes behave similarly in both reactions 20, 21). 

The reactions of purine ribonucleotide interconversion may be arranged in two cycles which have inosinate as the common intermediate. One may ask exactly what is the function of these two cycles, into which there are so many points of entry the question may also be asked whether these pathways actually function in a cyclic manner. 

The activities of the enzymes of purine ribonucleotide interconversion can be both stimulated and inhibited in a variety of ways, and these potential control mechanisms may function not only to regulate the synthesis of ATP and of GTP, but also to maintain a balance in the relative intracellular concentrations of these two nucleotides. 

As a redox couple, proline and pyrroline-5-carboxylate provide a mechanism for the intercompartmental and intercellular transfer of redox potential. The transfer of redox potential alters the ratio of NADP /NADPH thereby activating certain metabolic pathways. Although the reduction of pyrroline-5-carboxylate is the central mechanism in the transfer of redox potential, the metabolic interconversions of proline, ornithine, and glutamate with pyrroline-5-carboxylate as the obligate intermediate also may play a role. The endpoint of this regulation appears to be the formation of purine ribonucleotides by both salvage and de novo mechanisms. Proline and pyrroline-5-carboxylate appear to be metabolic signals which can be fine-tuned by humoral factors to coordinate the metabolism of amino acids and ribonucleotides. When the transfer is from cell to cell, proline and pyrroline-5-carboxyl-ate can function as intercellular communicators. 

Biosynthesis and function of RNA - Mcmy inhibitors of RNA synthesis, such as aotinomycin, act by complexing with DNA and inhibiting its template function in the biosynthesis of RNA.3 Base analogs, such as 6-mercapto-purine and 8-azaguanine, interfere with interconversions of ribonucleotide subunits and inhibit novo synthesis of RNA.3 Utilization of these biochemical pathways for the design of chemotherapeutic agents is limited by considerations similar to those discussed for inhibitors of DNA synthesis. 

In summary, the biochemical function of folate coenzymes is to transfer and use these one-carbon units in a variety of essential reactions (Figure 2), including de novo purine biosynthesis (formylation of glycinamide ribonucleotide and 5-amino-4-imidazole carboxamide ribonucleotide), pyrimidine nucleotide biosynthesis (methylation of deoxyuridylic acid to thy-midylic acid), amino-acid interconversions (the interconversion of serine to glycine, catabolism of histidine to glutamic acid, and conversion of homocysteine to methionine (which also requires vitamin B12)), and the generation and use of formate. 

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See also in sourсe #XX -- [ ]

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