Hypoxanthine formation from adenine

The formation of purine from ammonium formiate (NH4+HCOO ), again a product of hydrolysis of HCN, was reported by Zubay and co-workers [75]. Treatment of AICN and AICA with a concentrated solution of NH4+HCOCT at 93 °C afforded adenine 1 and hypoxanthine 2, respectively (Scheme 8). A reaction pathway in which formate and ammonium ions were both reactants has been hypothesized for the formation of adenine. 

It cannot be ruled out that RNA transcription is unimportant for normal development prior to blastocyst formation. The fertilized egg contains many enzymes, and the activity of these has been shown to change considerably through preimplantation development. For example, the activity of hypoxanthine-guanine phosphoribosyltransferase, adenine phosphoribosyltransferase, and hexokinase increases markedly from the fertilized egg to the blastocyst stage (Brinster, 1968a Epstein, 1970) ... 

The molyhdopterin cofactor, as found in different enzymes, may be present either as the nucleoside monophosphate or in the dinucleotide form. In some cases the molybdenum atom binds one single cofactor molecule, while in others, two pterin cofactors coordinate the metal. Molyhdopterin cytosine dinucleotide (MCD) is found in AORs from sulfate reducers, and molyhdopterin adenine dinucleotide and molyb-dopterin hypoxanthine dinucleotide were reported for other enzymes (205). The first structural evidence for binding of the dithiolene group of the pterin tricyclic system to molybdenum was shown for the AOR from Pyrococcus furiosus and D. gigas (199). In the latter, one molyb-dopterin cytosine dinucleotide (MCD) is used for molybdenum ligation. Two molecules of MGD are present in the formate dehydrogenase and nitrate reductase. 

Biosynthetically, purines are built up via formation of the imidazole ring first, from glycine and formate, and thence to hypoxanthine and then the other natural purines. In the laboratory, most imidazole-based purine syntheses start with 5-aminoimidazole-4-carboxylic acid, particularly its amide (known by the acronym AICA), which as well as its riboside, is commercially available from biological sources. The use of 5-aminoimidazole-4-carbonitrile in this approach results in the formation of 6-amino-purines, as in a synthesis of adenine itself." ... 

When RNA of tobacco mosaic virus is incubated with nitrous acid, changes occur in the base composition because nitrous acid deaminates cytosine and adenine. (It also deaminates guanine, but not in the intact virus.) Cytosine is converted to uracil and adenine is converted to hypoxanthine (adenylic acid inosinic acid). Consequently, the six amino groups of adenine and cytosine are replaced by keto groups. Since the complementariness of the newly synthesized RNA chain is dictated by the formation of hydrogen bonds with the bases in the template, the newly synthesized RNA is different from the wild RNA and thus a base mutation has been introduced experimentally. 

Amino-4-imidazole carboxamide ribotide, a precursor only two steps removed (formylation and cycli-zation) from inosinic acid, can be synthesized by the direct condensation of the imidazole with 5-phosphori-bosyl pyrophosphate. The enzyme catalyzing this reaction was purified from an acetone powder of beef liver. The same enzyme (AMP pyrophosphorylase) catalyzes the condensation of adenine, guanine, and hypoxan-thine. Nucleoside phosphorylase is an enzyme that catalyzes the formation of a ribose nucleoside from a purine base and ribose-1-phosphate. Guanine, adenine, xanthine, hypoxanthine, 2,6-diaminopurine, and aminoimidazole carboxamide are known to be converted to their respective nucleosides by such a mechanism. In the presence of a specific kinase and ATP, the nucleoside is then phosphorylated to the corresponding nucleotide. 

Uric Add Formation. In vertebrates purines are oxidized to uric acid. This reaction is catalyzed by xanthine oxidase (or dehydrogenase), which attacks both hypoxanthine and xanthine.Since adenine and guanine nucleotides can give rise to the hydroxylated purines either as the nucleotide, nucleoside, or free base, all of the naturally occurring purines of animals can be converted to uric acid. Adenine may also be oxidized to 2,8-dihydroxy-4-aminopurine, which is excreted in the urine. The formation of uric acid from any of its precursors is followed conveniently spectrophotometrically (Fig. 29). ... 

A consideration of the possible pathways to account for nucleoside utilization indicated that the results could not be explained by the formation of hypoxanthine or adenine from the nucleosides. Hypoxanthine... 

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