Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P47989 (xanthine oxidase)
 8,633 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenosine produced from 5'-AMP has been proposed as a mediator of intrinsic renal regulation. The rates of 5'-AMP and adenosine metabolism are dependent on the activities of enzyme involved in purine metabolism. The activities of adenosine kinase (AK), adenosine deaminase (ADA), 5'-nucleotidase (5'-NT), AMP deaminase, xanthine oxidase and purine nucleoside phosphorylase were measured in cytosolic and membrane fractions from glomeruli, cortical tubules, medullary thick ascending limb of Henle (MTAL) and collecting duct prepared from rat kidney by combinations of sieving and sucrose density gradient centrifugation techniques. In the cytoplasm of glomeruli cells, the activity ratios of ADA/AK and AMP deaminase/5'-NT were 70 and 2.4, respectively. The highest activity of 5'-NT was found in membrane fractions of cortical tubules where it was equally distributed between luminal and antiluminal membranes. Membrane fractions of MTAL did not contain detectable amounts of adenosine deaminase activity. The highest activity of xanthine oxidase and purine nucleoside phosphorylase was in the cytoplasm fraction of glomeruli. These results suggest that deamination of AMP and adenosine may be favored in the cytoplasm of glomeruli cells. In contrast, in the extracellular space of glomeruli and especially in the cortical tubule, AMP can be converted preferentially to adenosine by 5'-NT.
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PMID:The distribution of enzymes involved in purine metabolism in rat kidney. 161 Aug 88

The enzymatic inosine 5'-monophosphate assay described by Grassl [in, Methods of Enzymatic Analysis (H. U. Bergman, ed.), pp. 2168-2171, Academic Press, New York (1974)] is highly nonspecific, as ITP, ATP, ADP, AMP, and adenosine react stoichiometrically. The reactivity with the adenine derivatives is due to the tri- and diphosphatase activity of alkaline phosphatase (AP), coupled with adenosine deaminase (and possibly AMP deaminase) contamination of commercially available preparations of AP, purine-nucleoside phosphorylase, and/or xanthine oxidase. The inclusion of coformycin (0.05 microgram/ml), a potent inhibitor of these deaminases, completely eliminated the cross-reactivity. ITP, however, still reacted stoichiometrically due to the tri- and diphosphatase activity of AP. Meyer and Terjung [Amer. J. Physiol. 237 C111-C118 (1979)] introduced a modification of Grassl's procedure, substituting 5'-nucleotidase for AP. It has been found that this disallows reactivity with ATP, ADP, and ITP but that AMP and adenosine still react completely. Coformycin prevents this cross-reactivity. It is therefore recommended that the assay be carried out with 5'-nucleotidase (instead of AP) and coformycin, in order to achieve a more specific assay, and one more suitable for use with whole tissue extracts.
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PMID:An enzymatic inosine 5'-monophosphate assay of increased specificity. 298 81

In cancer cells, a marked imbalance in the enzymic pattern of purine metabolism is linked with transformation and/or progression. In chemically-induced, transplantable hepatomas in rat, the specific activities of the anabolic enzymes, IMP dehydrogenase, GMP synthetase, adenylosuccinate synthetase, adenylosuccinase, AMP deaminase and amidophosphoribosyltransferase, increased to 13.5-, 3.7-, 3.1-, 1.8-, 5.5- and 2.8-fold, respectively, of those in normal liver. Activities of the catabolic enzymes, inosine phosphorylase, xanthine oxidase and uricase, decreased to 19, 10 and 4%, respectively. This enzymic imbalance was specific to hepatic neoplasia, since no similar pattern was observed in differentiating or regenerating liver. Most enzymic alterations were present also in chemically- and virus-induced animal tumors, in human kidney, liver and colon carcinomas, and in human colon carcinoma xenografts. The molecular correlation concept applies to purine biochemistry and an important segment of neoplastic gene expression was identified in the behavior of key purine-metabolizing enzymes.
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PMID:Enzymes of purine metabolism in cancer. 686 38

The perfused rat hindlimb preparation was used with a blood cell-free perfusate to investigate alterations in the purine nucleotide metabolism, flow rate, perfusion pressure, and venous excretion in response to ischemia and ischemia followed by reperfusion in skeletal muscle. The development of a physical hindrance during postischemic reperfusion, indicated by an increase in reperfusion pressure and a decrease in flow rate, coincided with a 90% decrease in phosphocreatine and a 50-70% reduction in total adenine nucleotide pool. The reflow impairment could not be explained by blood cell plugging of the capillaries. Washout of several metabolites was demonstrated during reperfusion. Hypoxanthine accumulated intracellularly during ischemia, and a substantial amount of uric acid was excreted into the venous effluent during reperfusion. The experimental data were fitted into a computer simulation model of the purine pathways. The model indicated that AMP deaminase was the predominant enzymatic pathway for the AMP degradation. It was demonstrated that ATP preferably accumulated as inosine-5'-monophosphate during ischemia and that xanthine oxidase was undetectable in skeletal muscle tissue homogenates. However, vascular endothelial cell xanthine oxidase activity responsible for a free radical-induced reperfusion injury could not be excluded.
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PMID:Purine metabolic pathways in rat hindlimb perfusion model during ischemia and reperfusion. 823 94

Hepatocytes are affected by many cytokines and growth factors during liver regeneration. In regenerating rat liver cells cultures, liver cell growth factor (LCGF), hepatic stimulator substance (HSS), interleukin-1 beta (IL-1 beta), as well as their combination, were tested for their ability to activate the enzymes involved in purine metabolism. The enzymes tested were 5' nucleotidase, AMP deaminase, adenosine deaminase and xanthine oxidase. The cytokines alone or in combination, activated 5' nucleotidase and adenosine deaminase. Activity of AMP deaminase was stimulated by IL-1 beta associated with LCGF, HSS and IL-1 beta. Xanthine oxidase was stimulated by IL-1 beta but not with HSS and LCGF. Associated with IL-1 beta these two substances decreased its activity. A novel approach to the understanding of the mechanisms involved in the regulation of purine metabolism during liver regeneration, is proposed.
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PMID:Effects of growth factors on the enzymes of purine metabolism in culture of regenerating rat liver cells. 869 4

Many enzymes are involved in the biosynthesis, interconversion, and degradation of purine compounds. The exact function of these enzymes is still unknown, but they seem to play important roles other than in purine metabolism. To elucidate their functional roles, it is imperative to clarify their tissue distribution at the cellular or subcellular level. The present review summarizes the currently available information about their histochemical localization and proposed functions. In general, 5'-nucleotidase has been considered as a marker enzyme for the plasma membrane, and is considered to be a key enzyme in the generation of adenosine, a potential vasodilator. However, from its wide range of localization in tissues it is also considered to be related to the membrane movement of cells in the transitional epithelium, cellular motile response, transport process, cellular growth, synthesis of fibrous protein and calcification, lymphocyte activation, neurotransmission, and oxygen sensing mechanism. Adenosine deaminase (ADA) is present in all tissues in mammals. Although the main function of ADA is the development of the immune system in humans, it seems to be associated with the differentiation of epithelial cells and monocytes, neurotransmission, and maintenance of gestation. Purine nucleoside phosphorylase (PNP) is generally considered as a cytosolic enzyme, but recently, mitochondrial PNP, a different protein from cytosolic PNP, was reported. PNP is also widely expressed in human tissues. It is found in most tissues of the body, but the highest activity is in peripheral blood granulocyte and lymphoid tissues. It is also related to the development of T-cell immunity in humans as is ADA. Moreover, its contribution to centriole replication and/or regulation of microtubule assembly has been suggested. Immunohistochemical localization of xanthine oxidase has been reported in various tissues from various animal species. Xanthine oxidase has been suggested to be involved in the pathogenesis of post-ischemic reperfusion tissue injury through the generation of reactive oxygen species, while the extensive tissue localization of xanthine dehydrogenase/oxidase suggests several other roles for this enzyme, including a protective barrier against bacterial infection by producing either superoxide radicals or uric acid. Furthermore, an involvement in cellular proliferation and differentiation has been suggested. Urate oxidase is generally considered a liver-specific enzyme, except for bovines which possess this enzyme in the kidney. Urate oxidase is exclusively located in the peroxisomes of fish, frogs, and rats, but was lost in birds, some reptiles, and primates during evolution. A histochemical demonstration of allantoin-degrading enzymes has not been performed, but these enzymes have been located in peroxisomes by sucrose density gradient centrifugation. AMP deaminase activity is higher in skeletal muscle than in any other tissues. AMP deaminase may be involved in a number of physiological processes, such as the conversion of adenine nucleotide to inosine or guanine nucleotide, stabilizing the adenylate energy charge, and the reaction of the purine nucleotide cycle. There are three distinct isozymes (A, B, C) with different kinetic, physical, and immunological properties. Isozymes A, B, C have been isolated from muscle, liver (kidney), and heart tissue, respectively. In the muscle, AMP deaminase isozymes exist in a different part, suggesting a multiple functional role of this enzyme. High hypoxanthine-guanine phosphoribosyltransferase (HGPRT) activity is found in some regions of a normal adult human brain. However, very little is known regarding the histochemical tissue localization of HGPRT. Immunohistochemical localization of its developmental expression suggests that HGPRT may not be essential for purine nucleotide supplement in the segmentation of brain cells, but may play a significant role in the developing hippocampus.
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PMID:Enzymes involved in purine metabolism--a review of histochemical localization and functional implications. 1050 47

L-arginine is conditionally essetcial amino acid, required for normal cell growth, protein synthesis, ammonia detoxification, tissue growth and general performance, proposed in the treatment of men sterility and prevention of male impotence. The aim of the present paper was to estimate the activity of the enzymes of adenine nucleotide metabolism: 5'-nucleotidase (5'-NU), adenosine deaminase (ADA), AMP deaminase, and xanthine oxidase (XO), during dietary intake of L-arginine for a period of four weeks of male Wistar rats. Adenosine concentration in tissues is maintained by the relative activities of the adenosine-producing enzyme, 5'-NU and the adenosine-degrading enzyme-ADA adenosine deaminase. Dietary L-arginine intake directed adenine nucleotide metabolism in liver, kidney, and testis tissue toward the activation of adenosine production, by increased 5'-NU activity and decreased ADA activity. Stimulation of adenosine accumulation could be of importance in mediating arginine antiatherosclerotic, vasoactive, immunomodulatory, and antioxidant effects. Assuming that the XO activity reflects the rate of purine catabolism in the cell, while the activity of AMP deaminase is of importance in ATP regeneration, reduced activity of XO, together with the increased AMP-deaminase activity, may suggest that adenine nucleotides are presumably directed to the ATP regenerating process during dietary L-arginine intake.
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PMID:L-arginine intake effect on adenine nucleotide metabolism in rat parenchymal and reproductive tissues. 2262 85

Maternal metabolic diseases increase offspring risk for low birth weight and cardiometabolic diseases in adulthood. Excess fructose consumption may confer metabolic risks for both women and their offspring. However, the direct consequences of fructose intake per se are unknown. We assessed the impact of a maternal high-fructose diet on the fetal-placental unit in mice in the absence of metabolic syndrome and determined the association between maternal serum fructose and placental uric acid levels in humans. In mice, maternal fructose consumption led to placental inefficiency, fetal growth restriction, elevated fetal serum glucose and triglyceride levels. In the placenta, fructose induced de novo uric acid synthesis by activating the activities of the enzymes AMP deaminase and xanthine oxidase. Moreover, the placentas had increased lipids and altered expression of genes that control oxidative stress. Treatment of mothers with the xanthine oxidase inhibitor allopurinol reduced placental uric acid levels, prevented placental inefficiency, and improved fetal weights and serum triglycerides. Finally, in 18 women delivering at term, maternal serum fructose levels significantly correlated with placental uric acid levels. These findings suggest that in mice, excess maternal fructose consumption impairs placental function via a xanthine oxidase/uric acid-dependent mechanism, and similar effects may occur in humans.
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PMID:Maternal fructose drives placental uric acid production leading to adverse fetal outcomes. 2712 96