Oxypurines

Woolfolk CA, BS Woolfolk, HR Whiteley (1970) 2-oxypurine dehydrogenase from Micrococcus aerogenes. I. 

Buhl, M.R. and Jorgensen, S. (1975). Breakdown of 5 -adenine nucleotides in ischaemic renal cortex estimated by oxypurine excretion during perfusion. Scand. J. Clin. Lab. Invest. 35, 211-217. 

Letham, D. S. A 6-oxypurine with growth promoting activity. Plant Sci Lett 1982 26 241-249. 

The enzyme has been isolated from both eukaryotic and prokaryotic organisms [2] and functions in the purine salvage pathway [1,3]. Purine nucleoside phosphorylase isolated from human erythrocytes is specific for the 6-oxypurines and many of their analogs [4] while PNPs from other organisms vary in their specificity [5]. The human enzyme is a trimer with identical subunits and a total molecular mass of about 97,000 daltons [6,7]. Each subunit contains 289 amino acid residues. 

L = 9-methyl-6-oxypurine purines, trans-H20 s, weak frans-axial ... 

The results of the calculations on a number of essential electronic properties of oxypurines are presented in Table XIII and are compared, as far as possible, with the available experimental data. They indicate the following. 

If desoxy-compounds are suitably oxidized, they lose two atoms of hydrogen and pass into oxypurins. 3-Methyldes-oxyxanthine is thus converted into 3-methyl-2-oxypurin ... 

Dimethyl-2-oxypurin is formed on oxidation with an excess of silver acetate. 

This is a compound which corresponds to the 3-methyl-2 oxypurin obtained from 3-methyldesoxyxanthine. Its strongly basic properties are conditioned by the methyl group in position (1). It may be here mentioned that Tafel has worked out his valuable method chiefly by the use of caffeine. The corresponding investigation has already been considered (p. 24 and p. 52). 

This substance is isomeric -with adenine and is verj> simjj lax to it. Nitrous acid converts it into 2-oxypurin, an isomer of hypoxanthine. 

The bases found in RNA (ribonucleic acid) are the purine heterocyclics adenine (6-aminopurine) and guanine (2-amino-6-oxypurine) and their complementary pyrimidine bases uracil (2,4-dioxypyrimidine) and cytosine (2-oxy-4-aminopyrimidine), respectively (Section 1, Appendix). In RNA double-stranded duplexes adenine (A) base-pairs with uracil (U) via two hydrogen bonds (A=U) and guanine base-pairs with cytosine (C) via 3 hydrogen bonds (G=C). Adenine forms the nucleoside adenosine by an N-glycosidic link with the... 

Traditionally, oxypurines aUantoin, uric acid, and, in some cases, xanthines have been analyzed in biofluids by colorimetric methods. 

Clearly, the determination of such compounds is crucial for diagnosis and monitoring of renal disease and metabolic disorders. The concentration of oxypurines in blood serum is among the most important parameters in biochemistry and clinical chemistry. Determination of uric acid is performed by enzymatic methods or colori-metrically by reduction of phosphotungstate. 

Guanine (2-amino-6-oxypurine) Guanosine Deoxyguanosine Guanosine monophosphate (GMP) Deoxyguanosine monophosphate (dGMP)... 

Hypoxanthine (6-oxypurine) Inosine Deoxyinosine Inosine monophosphate (IMP) Deoxyinosine monophosphate (dIMP)... 

The physiological role of the oxypurines is not completely understood, but certain facts have been amply confirmed. There are many pathological or physiologically abnormal conditions which can lead to concomitant alterations in the metabolism of these compounds. Under certain condi-... 

Purines are integral components of various fundamental biological entities. Their production and function are vital to all life. One of the most disturbing aspects of studies of oxypurines in man, however, is the fact that one can find little evolutionary advantage to modern man in the production of these compounds. The products are inherently dangerous because of their low solubility. Their synthesis does not seem to be a necessary by-product of a vital biochemical reaction, and their production results in the ultimate loss from the body of purine moieties that were produced at great biochemical expense. Nevertheless, they are very much a fact of life, the study of which is of fundamental significance. 

Oxypurines are end products of purine metabolism in man. They do not serve as a general end product of nitrogen, as is the case with some... 

There have been reports in the literature of hypouricemia coincident with specific inborn metabolic errors, but many of these cases are attributable to defects in the kidney leading to failure of renal tubular reabsorption. It was mentioned above that the excretion of uric acid by the Dalmatian coach hound can be attributed to such a mechanism (Fll). Similarly, the hypouricemia found in the Fanconi syndrome (L4) and Wilson s disease (B12) can be attributed to kidney malfunction. These are not true examples of underproduction of oxypurines, including uric acid, since the daily output of uric acid is normal. The large number of healthy people who have extremely low serum urate values, however, may indicate that there are individuals who underproduce oxypurines but suffer no ill effects because of this. The one well-documented inborn error that results in underproduction of uric acid is xanthinuria. It has been reported in relatively few cases, probably because individuals with this metabolic abnormality who suffer no ill effects would not come to the attention of a physician. 

The most common defect in oxypurine metabolism is that manifested by hypermicemia and hyperuricosuria. The many epidemiological investigations of uric acid levels have shown a distribution of serum uric acid values ranging from approximately 0.5 to 9.5 mg/100 ml of serum (E7, F6, N2). Many of the individuals with extreme levels are perfectly healthy, although there is a correlation between secondary complications and high uric acid values. ... 

This disease is of considerable interest in relation to oxypurine metabolism, although a wide variety of potential metabolic abnormalities have been said to be associated with it. In a review in 1961 Tickner (T4) asserted that there was evidence to support the postulate that psoriasis was associated with alterations in lipid, protein, carbohydrate, and mineral metabolism as well as in serum protein level. Investigators have since supported a myriad of hypotheses. Note has been taken of variations in carbohydrate metabolism (R16), and of changes in the synthesis of hyaluronic acid with resultant alterations in transport mechanisms (CIO). Changes in fatty acid levels and metabolism (C8), alterations of aldolase activity (C6), increased proteolytic activity (S33), and alterations in the composition of proteins in psoriatic scales (L20) have been suggested. Changes in serum copper content in psoriatic patients have been observed (L18). 

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