Purine 3- oxide

The purine 3-oxides (69JBC(244)4072, 70MI40905) and 7-oxides (76JOC1889) have potent oncogenic properties. 

Bromo-, 6-iodo-, 6-methoxy-, 6-sulfo-purines, 3-oxides 6-Bromo-, 6-iodo-, 6-methoxy, 6-sulfo-purines Ni/H2/aq. NH3/I h 69JOC2157... 

Purine 3-oxide has been prepared in good yield (64%) by hydrolysis of purine-6-sulfonic acid 3-oxide with 90% formic acid (B-78Ml40901,p. 33). Guanine 3-oxide may be obtained directly from guanine and hydrogen peroxide in trifluoroacetic acid and when boiled with 6N hydrochloric acid it readily produced xanthine 3-oxide (69JOC978). 6-Chloropurine... 

Non-microsomal oxidations may be subdivided into amine oxidation, alcohol and aldehyde oxidation, dehalogenation, purine oxidation, and aromatization. 

Purine oxidation. The oxidation of purines and purine derivatives is catalyzed by xanthine oxidase. For example, the enzyme oxidizes hypoxanthine to xanthine and thence uric acid (Fig. 4.34). Xanthine oxidase also catalyzes the oxidation of foreign compounds, such as the nitrogen heterocycle phthalazine (Fig. 4.35). This compound is also a substrate for aldehyde oxidase, giving the same product. 

Mercaptopurine and thioguanine are both given orally (Table 55-3) and excreted mainly in the urine. However, 6-MP is converted to an inactive metabolite (6-thiouric acid) by an oxidation catalyzed by xanthine oxidase, whereas 6-TG requires deamination before it is metabolized by this enzyme. This factor is important because the purine analog allopurinol, a potent xanthine oxidase inhibitor, is frequently used with chemotherapy in hematologic cancers to prevent hyperuricemia after tumor cell lysis. It does this by blocking purine oxidation, allowing excretion of cellular purines that are relatively more soluble than uric acid. Nephrotoxicity and acute gout produced by excessive uric acid are thereby prevented. Simultaneous therapy with allopurinol and 6-MP results in excessive toxicity unless the dose of mercaptopurine is reduced to 25% of the usual level. This effect does not occur with 6-TG, which can be used in full doses with allopurinol. 

The reaction mechanism is incompletely understood. Molybdenum, an essential cofactor, is the initial acceptor of electrons during purine oxidation and undergoes reduction from Mo + to Mo" +. Deficiency of molybdenum can result in xanthinuria. The electrons from molybdenum are passed successively to the iron-sulfur center, to FAD, and finally to oxygen. The oxygen incorporated into xanthine and uric acid originates in water. Xanthine oxidase also yields the superoxide radical, O2, which is then converted to hydrogen peroxide by superoxide dismutase (Chapter 14). This may yield free radicals,... 

Other DNA glycosylases recognize and remove a variety of damaged bases, including formamidopyrimidine and 8-hydroxyguanine (both arising from purine oxidation), hypoxanthine (arising from adenine deamination), and alkylated bases such as 3-methyladenine and... 

Scheme 5.3 Mechanism for purine oxidation at the XO/XDH active site.

Alkaloids derived from purine (10-36) and purine oxidation product xanthine (10-37), respectively, are called purine alkaloids. Purine alkaloids are the most widespread alkaloids in foods. 

Purine oxidation Incorporation of label from purine bases and nucleotides into ureides was first demonstrated in leaves of Acer saccharinum when [8- C]adenine was converted to a mixture of ALN, ALA, and urea, with some label occurring in xanthine and hypoxanthine (Barnes, 1959). Cell-free extracts of cowpea nodules converted labeled guanine or hypoxanthine into a mixture... 

Fig. 7. Model for the subcellular localization of reactions of purine synthesis and ureide biogenesis in nodules of ureide-exportlng legumes. The model is based on results of subcellular fractionation and ultrastructural studies. The processes (shown in the hatched boxes) involved in ureide biogenesis (i.e., nitrogen fixation, ammonium assimilation, precursor synthesis, purine synthesis, energy-yielding metabolism, and purine oxidation and catabolism) may occur in more than one subcellular compartment. The location of the enzymes involved in the conversion of IMP to xanthine is not certain. We have proposed that in soybean nodules these reactions [shown in bold-face type with bold arrows] occur in the plastid while in other species such as cowpea these reactions may take place in the ground cytoplasm. In all cases the intermediate exported from the plastid is uncertain. This uncertainty is indicated with the dashed lines and question marks.

Rainbird and Atkins (1981) suggested that uncase activity and the rate of purine oxidation might be controlled by Oj levels because of the high for O2... 

The net cost of purine synthesis is 19 ATP equivalents for ATP and reductant and 24 ATP equivalents for the carbon skeleton (total = 43). Thirteen and a half of these are recovered during the synthesis of glycine and methenyltetrahy-drofolate and the reoxidation of fumarate (via frimarase and malate dehydrogenase) and another 6 through purine oxidation (total = 19.5 net cost = 43 — 19.5 = 23.5). On the other hand the production of CIT costs 15 equivalents for ATP and reductant and 25 for the carbon skeleton (assumes production of oxoglutarate from 2 mol PGA —7 ATP equivalents for ATP and 2 NADH formed) for a total cost of 40 ATPs (13.3 per nitrogen). The reactions involved in CIT synthesis [Eqs. (22a-e)j are summarized in Eq. (22f). 

This enzyme, sometimes also called the Schardinger enzyme, occurs in milk. It is capable of " oxidising" acetaldehyde to acetic acid, and also the purine bases xanthine and hypoxanthine to uric acid. The former reaction is not a simple direct oxidation and is assumed to take place as follows. The enzyme activates the hydrated form of the aldehyde so that it readily parts w ith two hydrogen atoms in the presence of a suitable hydrogen acceptor such as methylene-blue the latter being reduced to the colourless leuco-compound. The oxidation of certain substrates will not take place in the absence of such a hydrogen acceptor. 

It has been stated that many halogen-free compounds, e.g., certain derivatives of pyridine and quinoline, purines, acid amides and cyano compounds, when ignited on copper oxide impart a green colour to the dame, presumably owing to the formation of volatile cuprous cyanide. The test is therefore not always trustworthy. The test is not given by duorides. 

Mechanistic aspects of the action of folate-requiring enzymes involve one-carbon unit transfer at the oxidation level of formaldehyde, formate and methyl (78ACR314, 8OMI2I6OO) and are exemplified in pyrimidine and purine biosynthesis. A more complex mechanism has to be suggested for the methyl transfer from 5-methyl-THF (322) to homocysteine, since this transmethylation reaction is cobalamine-dependent to form methionine in E. coli. 

Purine, 2-acetamido-6-benzyIthio-dihydrofuranylation, 5, 536 Purine, 8-aIkenyI-synthesis, 5, 537 Purine, 6-aIkoxy-oxidation, S, 539 Purine, I-aIkoxy-9-aIkyI-6-imino-... 

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