Guanine metabolism

Bl. Balis, M. E., Studies on the metabolism of human tumors. IV. Certain aspects of guanine metabolism. Cancer Res. 19, 297-302 (1959). 

The simple purine salvage scheme of the mucosal pathogens Giardia, Trichomonas, and Entamoeba species) with the lack of crossover from adenine to guanine metabolism means that there is an absolute requirement for each of these purines. This suggests that inhibition of either pathway will inhibit the organisms growth (Chapter 6). 

One of the steps in the metabolic degradation of guanine is hydrolysis lo give xanthine. Propose a mechanism. 

Temozolomide undergoes spontaneous hydrolysis and decarboxylation at physiological pH value and thereafter a methyldiazonium ion is released. This ion forms DNA adducts within guanine rich DNA sequences. Temozolomide has high bioavailability and is metabolized in the liver. 

Sulphonamides are structural analogues of PABA. They competitively inhibit the incorporation of PABA into dihydropteroic acid and there is some evidence for their incorporation into false folate analogues which inhibit subsequent metabolism. The presence of excess PABA will reverse the inhibitory action of sulphonamides, as will thymine, adenine, guanine and methionine. However, these nutrients are not normally available at the site of infections for which the sulphonamides are used. 

The liver RNA isolated from rats treated with C-NHEX yielded 1,6-hexanediol upon hydrolysis with acid (54). This result indicates that NHEX underwent metabolic a-hydroxylation to give an adduct that may have been formed at 0 of guanine. The initially formed adduct would have been expected to be a 6-oxo-hexyl derivative reduction of the adduct must have occurred in order to produce the observed 1,6-hexanediol. 

In the first family, the metal is coordinated by one molecule of the pterin cofactor, while in the second, it is coordinated to two pterin molecules (both in the guanine dinucleotide form, with the two dinucleotides extending from the active site in opposite directions). Some enzymes also contain FejSj clusters (one or more), which do not seem to be directly linked to the Mo centers. The molybdenum hydroxylases invariably possess redox-active sites in addition to the molybdenum center and are found with two basic types of polypeptide architecture. The enzymes metabolizing quinoline-related compounds, and derivatives of nicotinic acid form a separate groups, in which each of the redox active centers are found in separate subunits. Those enzymes possessing flavin subunits are organized as a2jS2A2, with a pair of 2Fe-2S centers in the (3 subunit, the flavin in the (3 subunit, and the molybdenum in the y subunit. 

Uric acid is a normal product of metabolism. The chemistry of the purines, the uric acid syntheses of Baeyer and Fischer, Behrend and Roosen, and W. Traube, the chemistry of adenine, guanine, caffeine, and their relationships to uric acid, should be studied. 

Purines A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric add is the metabolic end product of purine metabolism. [NIH]... 

Brimer PA, Tan EL, Hsie AW. 1981. Effect of metabolic activation on the mutagenicity and cytotoxicity of ethylene dibromide in the Chinese hamster ovary hypoxanthine guanine phosphoribosyl transferase [Abstract]. Environ Mutagen 3 317-318. 

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