Xanthine Dehydrogenase Levels Research Articles

Integrated microbiome and metabolome analysis reveals the key role of taurohyocholate in the treatment of hyperuricemia with Lacticaseibacillus rhamnosus 2016SWU.05.0601

The incidence of hyperuricemia (HUA) is on the rise, posing a significant threat to human health. Several probiotics have shown potential in treating HUA; however, the critical role of intestinal metabolites in this therapy remains inadequately understood. Our study demonstrated that Lacticaseibacillus rhamnosus 2016SWU.05.0601 not only reduced the expression levels of xanthine dehydrogenase and the content and activity of xanthine oxidase in the liver but also regulated the uric acid transporters expression in the kidney, thereby attenuating HUA in mice. Additionally, L. rhamnosus 2016SWU.05.0601 modulated the gut microbiota and metabolite abundance in HUA mice. Correlation analysis revealed that the gut microbiota metabolite taurohyocholate played a vital role in the treatment of HUA by L. rhamnosus 2016SWU.05.0601, as confirmed in HUA cell models. Our research provides a significant theoretical basis for elucidating the mechanisms by which probiotics alleviate HUA and for developing functional ingredients for HUA treatment.

Clinical Significance of Elevated Xanthine Dehydrogenase Levels and Hyperuricemia in Patients with Sepsis.

Patient outcomes for severe sepsis and septic shock remain poor. Excessive oxidative stress accelerates organ dysfunction in severe acute illnesses. Uric acid (UA) is the most abundant antioxidant. We hypothesized that UA and related molecules, which play a critical role in antioxidant activity, might be markers of oxidative stress in sepsis. The study aimed to clarify the clinical significance of UA and the relationship between UA, molecules related to UA, and outcomes by measuring blood UA, xanthine dehydrogenase (XDH), and 8-hydroxy-2-deoxyguanosine (8-OHdG) levels over time. Blood UA levels in septic patients were correlated with the SOFA score (ρ = 0.36, p < 0.0001) and blood XDH levels (ρ = 0.27, p < 0.0001). Blood XDH levels were correlated with the SOFA score (ρ = 0.59, p < 0.0001) and blood 8-OHdG levels (ρ = -0.32, p < 0.0001). Blood XDH levels were persistently high in fatal cases. Blood XDH level (OR 8.84, 95% CI: 1.42-91.2, p = 0.018) was an independent factor of poor outcomes. The cutoff of blood XDH level was 1.38 ng/mL (sensitivity 92.8%, specificity 61.9%), and those 1.38 ng/mL or higher were associated with a significantly reduced survival rate (blood XDH level > 1.38 ng/mL: 23.7%, blood XDH level < 1.38 ng/mL: 96.3%, respectively, p = 0.0007). Elevated UA levels due to elevated blood XDH levels in sepsis cases may reduce oxidative stress. Countermeasures against increased oxidative stress in sepsis may provide new therapeutic strategies.

Inhibition of Xanthine Oxidase Protects against Diabetic Kidney Disease through the Amelioration of Oxidative Stress via VEGF/VEGFR Axis and NOX-FoxO3a-eNOS Signaling Pathway.

Xanthine oxidase (XO) is an important source of reactive oxygen species. This study investigated whether XO inhibition exerts renoprotective effects by inhibiting vascular endothelial growth factor (VEGF) and NADPH oxidase (NOX) in diabetic kidney disease (DKD). Febuxostat (5 mg/kg) was administered to streptozotocin (STZ)-treated 8-week-old male C57BL/6 mice via intraperitoneal injection for 8 weeks. The cytoprotective effects, its mechanism of XO inhibition, and usage of high-glucose (HG)-treated cultured human glomerular endothelial cells (GECs) were also investigated. Serum cystatin C, urine albumin/creatinine ratio, and mesangial area expansion were significantly improved in febuxostat-treated DKD mice. Febuxostat reduced serum uric acid, kidney XO levels, and xanthine dehydrogenase levels. Febuxostat suppressed the expression of VEGF mRNA, VEGF receptor (VEGFR)1 and VEGFR3, NOX1, NOX2, and NOX4, and mRNA levels of their catalytic subunits. Febuxostat caused downregulation of Akt phosphorylation, followed by the enhancement of dephosphorylation of transcription factor forkhead box O3a (FoxO3a) and the activation of endothelial nitric oxide synthase (eNOS). In an in vitro study, the antioxidant effects of febuxostat were abolished by a blockade of VEGFR1 or VEGFR3 via NOX-FoxO3a-eNOS signaling in HG-treated cultured human GECs. XO inhibition attenuated DKD by ameliorating oxidative stress through the inhibition of the VEGF/VEGFR axis. This was associated with NOX-FoxO3a-eNOS signaling.

Female AhR Knockout Mice Develop a Minor Renal Insufficiency in an Adenine-Diet Model of Chronic Kidney Disease.

Cardiovascular complications observed in chronic kidney disease (CKD) are associated with aryl hydrocarbon receptor (AhR) activation by tryptophan-derived uremic toxins—mainly indoxyl sulfate (IS). AhR is a ligand-activated transcription factor originally characterized as a receptor of xenobiotics involved in detoxification. The aim of this study was to determine the role of AhR in a CKD mouse model based on an adenine diet. Wild-type (WT) and AhR−/− mice were fed by alternating an adenine-enriched diet and a regular diet for 6 weeks. Our results showed an increased mortality rate of AhR−/− males. AhR−/− females survived and developed a less severe renal insufficiency that WT mice, reflected by urea, creatinine, and IS measurement in serum. The protective effect was related to a decrease of pro-inflammatory and pro-fibrotic gene expression, an attenuation of tubular injury, and a decrease of 2,8-dihydroxyadenine crystal deposition in the kidneys of AhR−/− mice. These mice expressed low levels of xanthine dehydrogenase, which oxidizes adenine into 2,8-dihydroxyadenine, and low levels of the IS metabolism enzymes. In conclusion, the CKD model of adenine diet is not suitable for AhR knockout mice when studying the role of this transcription factor in cardiovascular complications, as observed in human CKD.

Goose astrovirus infection affects uric acid production and excretion in goslings

In 2018, a new goose astrovirus (GAstrV) was reported in China, which causes 2 to 20% deaths in 4- to 16-day-old goslings causing great damages to the livestock industry. Gout is the typical feature of GAstrV infection in goslings. However, the mechanism of gout formation remains unclear. In the present study, 2-day-old goslings were infected intramuscularly with GAstrV for 14 D. One quarter of the infected goslings died, and typical gout pathological changes were found in the dead infected goslings. Pathological changes were observed in the morphology of the kidney and liver, such as degeneration, necrosis, and inflammatory cell infiltration. Accordingly, a high virus load was found in both organs. The serum level of uric acid in the inoculated goslings was higher, whereas no differences were found in levels of creatinine, calcium, and phosphorus. Moreover, the xanthine dehydrogenase (XOD) and adenosine deaminase (ADA) activities and the mRNA levels of xanthine dehydrogenase, adenosine deaminase, phosphoribosyl pyrophosphate amidotransferase, and phosphoribosyl pyrophosphate synthetase 1 in livers increased, wheres the multidrug resistance–associated protein 4 mRNA level and Na-K-ATPase activity in the kidneys decreased. These results showed that GAstrV infection could cause lesions on the liver and kidney and then increase the expression or activity of enzymes related to uric acid production in the liver and decrease renal excretion function, which contribute to hyperuricemia and gout formation.

A pan-cancer study of the transcriptional regulation of uricogenesis in human tumours: pathological and pharmacological correlates.

Uric acid (UA) is the end product of the catabolism of purines, and its serum levels are commonly increased in cancer patients. We aimed to explore the transcriptional regulation of tumour uricogenesis in human tumours, and relate uricogenesis with tumour pathological and pharmacological findings. Using data from The Cancer Genome Atlas (TCGA), we analysed the expression levels of xanthine dehydrogenase (XDH) and adenine phosphoribosyltransferase (APRT), two key enzymes in UA production and the purine salvage pathway, respectively. We found large differences between tumour types and individual tumours in their expression of XDH and APRT. Variations in locus-specific DNA methylation and gene copy number correlated with the expression levels of XDH and APRT in human tumours respectively. We explored the consequences of this differential regulation of uricogenesis. Tumours with high levels of XDH mRNA were characterised by higher expression of several genes encoding pro-inflammatory and immune cytokines, and increased levels of tumour infiltration with immune cells. Finally, we studied cancer drug sensitivity using data from the National Cancer Institute-60 (NCI-60) database. A specific correlation was found between the expression levels of APRT and cell sensitivity to the chemotherapeutic agent 5-fluorouracil (5-FU). Our findings underline the existence of great differences in uricogenesis between different types of human tumours. The study of uricogenesis offers promising perspectives for the identification of clinically relevant molecular biomarkers and for tumour stratification in the therapeutic context.

Toxicities of selected medicinal plants and floras of lower phyla

The aim of this study was to evaluate the toxic effects associated with the administration of aqueous extracts (AE) of Calliandra portoricensis (CP), Dracaena arborea (DA), Duranta repens (DR), Polytrichum juniperinum (PJ), Parmelia caperata (PC), and Nostartium officinale (NO) on Wistar rats. LD50 for each plant was obtained prior to administration. Seven groups of six rats each were orally gavaged for 28 days as follows; group 1–7 received normal rat pellets and saline, in addition, group 2 received 20 mg/kg b.w CP, group 3 & 4 respectively received 8 mg/kg b.w DA and DR, group 5 & 6 respectively received 4 mg/kg b.w PJ and PC, and group 7 received 100 mg/kg b.w NO. Liver enzymes; ALP, ALT, AST and GGT were significantly (p < 0.05) elevated by CP, DR, PJ and PC extracts. All the extracts caused significant alterations of the total protein, albumin and globulin levels. The urea levels were deranged by all the extracts while CP, PJ, PC, and NO extracts caused no significant effects on the creatinine levels. Both DR and NO deranged the serum electrolytes; Na, K, Cl, and HCO3. Results for the lipid profile showed that all extracts significantly altered the phosphatidate phosphohydrolase and LDL levels while no significant effects were observed in the VLDL, TG, TC, HDL, cardiac risk ratio, arterogenic coefficients, and arterogenic index of plasma, of NO treated rats. For hematological parameters DR, PJ, and PC significantly deranged the RBC, HGB, MCHC, MCV, and MCH concentrations while the neutrophils, eosinophils and basophils were significantly altered on administration of all the extracts. No significant effects were observed on the platelets and plateletcrit level in rats gavaged with CP, whereas the MPV, PDW, and PCT concentrations were deranged by DR extracts. CP and NO caused no alterations in the MDA, GSH, and GST levels whereas the SOD, GPx, and xanthine oxidase levels were significantly deranged by all the plant extracts. Only NO treatment produced catalase, glutathione reductase, and xanthine dehydrogenase levels equivalent to the control group. This study has shown various degrees of deleterious effects on biochemical parameters associated with the consumption of these plants, thus raising serious concerns over their continuous applications as local medicaments.

Teneligliptin Decreases Uric Acid Levels by Reducing Xanthine Dehydrogenase Expression in White Adipose Tissue of Male Wistar Rats.

We investigated the effects of teneligliptin on uric acid metabolism in male Wistar rats and 3T3-L1 adipocytes. The rats were fed with a normal chow diet (NCD) or a 60% high-fat diet (HFD) with or without teneligliptin for 4 weeks. The plasma uric acid level was not significantly different between the control and teneligliptin groups under the NCD condition. However, the plasma uric acid level was significantly decreased in the HFD-fed teneligliptin treated rats compared to the HFD-fed control rats. The expression levels of xanthine dehydrogenase (Xdh) mRNA in liver and epididymal adipose tissue of NCD-fed rats were not altered by teneligliptin treatment. On the other hand, Xdh expression was reduced significantly in the epididymal adipose tissue of the HFD-fed teneligliptin treated rats compared with that of HFD-fed control rats, whereas Xdh expression in liver did not change significantly in either group. Furthermore, teneligliptin significantly decreased Xdh expression in 3T3-L1 adipocytes. DPP-4 treatment significantly increased Xdh expression in 3T3-L1 adipocytes. With DPP-4 pretreatment, teneligliptin significantly decreased Xdh mRNA expression compared to the DPP-4-treated 3T3-L1 adipocytes. In conclusion, our studies suggest that teneligliptin reduces uric acid levels by suppressing Xdh expression in epididymal adipose tissue of obese subjects.

Coronary Artery Superoxide Production and Nox Isoform Expression in Human Coronary Artery Disease

Oxidative stress plays important role in the pathogenesis of atherosclerosis and coronary artery disease (CAD). We aimed to determine the sources and selected molecular mechanisms of oxidative stress in CAD. We examined basal and NAD(P)H oxidase-mediated superoxide (O2*-) production using lucigenin chemiluminescence, ferricytochrome c and dihydroethidium fluorescence in human coronary arteries from 19 CAD and 17 non-CAD patients undergoing heart transplantation. NAD(P)H oxidase subunits and xanthine oxidase expression were measured. Superoxide production was greater in coronary arteries from patients with CAD, even in vessels without overt atherosclerotic plaques, and was doubled within branching points of coronary arteries. Studies using pharmacological inhibitors and specific substrates showed that NAD(P)H oxidases (60%) and xanthine oxidase (25%) are primary sources of O2*- in CAD. Losartan significantly inhibited superoxide production in coronary arteries. NAD(P)H oxidase activity and protein levels of the NADPH oxidase subunits p22phox, p67phox, and p47phox were significantly increased in CAD, as were mRNA levels for p22phox and nox2, and no NAD(P)H oxidase subunit mRNA levels correlated with NAD(P)H oxidase activity in vessels from individual patients. Activity and protein expression of xanthine oxidase were increased in CAD, whereas xanthine dehydrogenase levels were not changed. Increased expression and activity of NAD(P)H oxidase subunits and xanthine oxidase, in part mediated through angiotensin II and PKC-dependent pathways, are important mechanisms underlying increased oxidative stress in human coronary artery disease.

Xanthine oxidase activity in the dexamethasone-induced hypertensive rat

Hypertension may be associated with an increase in oxidative stress as a possible mechanism for the increased vascular tone and organ injury. Previously, we reported an increased production of reactive oxygen species and endothelial cell death in the microcirculation of hypertensive rats. We hypothesize that xanthine oxidase (XO) may be a potential source of oxidants induced by glucocorticoid-induced hypertension. Male Wistar rats were administered dexamethasone (0.5 mg/kg/day) for 5 days to induce hypertension. After general anesthesia, cremaster muscle was collected for analysis of XO and xanthine dehydrogenase (XDH) activities. The mean blood pressure and XO levels in cremaster muscle were significantly increased in the dexamethasone-treated rats compared with controls. There was a strong age-dependent rise in total XO + XDH activity in all groups. To inhibit XO, we administered allopurinol (ALLO, 0.4 mg/mL) in the drinking water to a subset of control and dexamethasone-treated rats during a 5-day treatment. The ALLO significantly reduced the mean arterial blood pressure in the dexamethasone-treated rats. Although in the cremaster muscle the total XO + XDH levels were not completely reduced with ALLO, the XO levels of the dexamethasone-treated + ALLO rats were reduced to levels of the control + ALLO group. These results suggest that dexamethasone induces an elevated level of XO activity in the cremaster muscle. The enhanced XO activity can be attenuated by chronic allopurinol treatment.

Xanthine dehydrogenase in the fat body of Manduca sexta: Purification, characterization, subcellular localization and levels during the last larval instar

Xanthine dehydrogenase was isolated and purified from the fat body of fifth instar tobacco hornworms, Manduca sexta (L.) by ammonium sulfate precipitation, Sephacryl S-400 gel filtration, QAE-Sephadex ion exchange chromatography and reactive blue-2 Sepharose affinity chromatography. The preparation appeared homogeneous following analysis by polyacrylamide disc gel electrophoresis, sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE), and rocket and crossed immunoelectrophoresis using rabbit antiserum against purified xanthine dehydrogenase. The molecular weight of native xanthine dehydrogenase was estimated at about 300,000 while SDS-PAGE indicated that the enzyme consisted of two 158,000 mol. wt subunits. Kinetic analyses revealed high affinities for xanthine and hypoxanthine as substrates. Electron acceptors (cofactors) included NAD +, as well as the dyes, p-iodonitrotetrazolium violet and nitro blue tetrazolium. A broad pH optimum was observed between pH 7 and 10, and xanthine dehydrogenase was competitively inhibited by allopurinol and irreversibly inhibited by the sulfhydryl inhibitor, p-hydroxymercuribenzoate. The levels of xanthine dehydrogenase in fat body extracts from fifth instar larvae, as determined by both enzyme assay and immunoelectrophoresis, decreased from days 1 to 5. Ultra-structural analysis of day 3 larval fat body cells by immunocytochemical techniques, using colloidal gold staining, revealed that xanthine dehydrogenase was specifically located either within urate storage vacuoles or near the basal lamina of the cells.

Role of Xanthine Oxidase in the Potentiation of Doxorubicin-Induced Cardiotoxicity by Mitomycin C

Clinical evidence has suggested that mitomycin C (MMC) potentiates doxorubicin (DOX) induced cardiotoxicity. In this study a mouse model was used to examine the effect of DOX on the ability of cardiac tissue to bioactivate MMC to generate oxygen radicals. Cardiac damage was assessed by measuring serum CPK-MB isoenzyme levels and thiobarbituric acid reactive substances (TBARS) in the cardiac tissue. The exposure of animals to DOX or DOX and MMC over a three week period led to an increase in serum CPK-MB isoenzyme levels as well as TBARS. Treatment with DOX led to an increase in MMC-dependent, NADH-dependent, cyanide insensitive oxygen consumption, compared to control animals, thereby suggesting increased MMC-dependent oxygen radical generation. Levels of xanthine oxidase (XO; EC 1.1.3.22) and NADPH:cytochrome C reductase, two enzymes known to bioactivate MMC with subsequent oxygen radical generation, were measured in cardiac tissue with a 4.5 x increase in XO activity seen in DOX treated animals vs controls and no change in NADPH:cytochrome C reductase activity. Cardiac levels of xanthine dehydrogenase (XDH; EC 1.1.1.204) activity in DOX treated animals decreased while the XO/XDH ratio increased, suggesting a conversion of XDH to XO following DOX treatment.

Molybdoenzymes in Drosophila. IV. Further characterization of the cinnamon phenotype

Mutations at the cin gene display drastically lowered levels of the molybdoenzymes, xanthine dehydrogenase (XDH) and aldehyde oxidase (AO), and lack pyridoxal oxidase (PO) and sulfite oxidase (SO) activities. Certain mutations at cin also display varying degrees of female sterility, which is maternally affected. Here we characterize five new cin alleles with respect to the molybdoenzyme activities as well as the molybdenum cofactor, commonly required for molybdoenzyme activity. In complementing cin heterozygotes we find that, in addition to the previously reported unusually high levels of XDH and AO activities, there are unusually elevated levels of SO activity, as well as complementation for PO activity. The levels of immunologically crossreacting material in such heterozygotes indicate that the elevated levels of molybdoenzyme activities cannot be due to increases in the number of enzyme molecules. Measurements of the level of molybdenum cofactor activity normally present in XDH, AO, PO, and SO point to the possibility that a larger fraction of the enzyme molecules are active in these heterozygotes. The possible role of SO with respect to cinnamon's female sterility is also discussed.

Xanthine oxidase-derived hydrogen peroxide contributes to ischemia reperfusion-induced edema in gerbil brains.

The contribution of toxic O2 metabolites to cerebral ischemia reperfusion injury has not been determined. We found that gerbils subjected to temporary unilateral carotid artery occlusion (ischemia) consistently developed neurologic deficits during ischemia with severities that correlated with increasing degrees of brain edema and brain H2O2 levels after reperfusion. In contrast, gerbils treated just before reperfusion (after ischemia) with dimethylthiourea (DMTU), but not urea, had decreased brain edema and brain H2O2 levels. In addition, gerbils fed a tungsten-rich diet for 4, 5, or 6 wk developed progressive decreases in brain xanthine oxidase (XO) and brain XO + xanthine dehydrogenase (XD) activities, brain edema, and brain H2O2 levels after temporary unilateral carotid artery occlusion and reperfusion. In contrast to tungsten-treated gerbils, allopurinol-treated gerbils did not have statistically significant decreases in brain XO or XO + XD levels, and reduced brain edema and brain H2O2 levels occurred only in gerbils developing mild but not severe neurologic deficits during ischemia. Finally, gerbils treated with DMTU or tungsten all survived, while greater than 60% of gerbils treated with urea, allopurinol, or saline died by 48 h after temporary unilateral carotid artery occlusion and reperfusion. Our findings indicate that H2O2 from XO contributes to reperfusion-induced edema in brains subjected to temporary ischemia.

Alteration of the gene for xanthine dehydrogenase in Drosophila following treatment with wildtype DNA.

Microinjection of whole genome DNA into Drosophila embryos can result in a variety of changes to the host genome. In the experiments reported here, wildtype DNA is injected into mutant animals lacking xanthine dehydrogenase activity by virtue of a mutation in the structural gene for the enzyme, the rosy gene. Animals with wildtype eye pigmentation and normal levels of xanthine dehydrogenase result from the treatment. Analysis of the electrophoretic mobility of the enzyme in the altered stocks indicates, in four of five cases, that the restoration of activity coincides with changes in electrophoretic mobility. The changes which occur are consistent with acquisition of sequence from the donor DNA and, in two cases, provide evidence for recombination between homologous sequences.

Enzymatic correlates and ontogeny of uricotelism in tree frogs of the genus Phyllomedusa

AbstractActivities of arginase, xanthine dehydrogenase, and uricase were measured in liver and kidney of adult Phyllomedusa sauvagei and P. hypochondrialis to examine the enzymatic basis of their unusual ability to excrete uric acid. Comparable values were obtained for two species of ureotelic anurans and a uricotelic lizard. Both Phyllomedusa species exhibited high hepatic and renal levels of xanthine dehydrogenase, whereas this enzyme was not detected in the livers of the ureotelic frogs or the lizard. Hepatic xanthine dehydrogenase was significantly higher in P. sauvagei, which excretes urate predominantly, than in P. hypochondrialis, which excretes 20% of its nitrogen as urate. Hepatic arginase was much lower in both Phyllomedusa species than in the ureotelic frogs, but higher than in the lizard. Reduced levels of uricase were also associated with uricotelism in this genus.Xanthine dehydrogenase was present in livers of larval P. sauvagei well in advance of the onset of uric acid excretion late in metamorphosis. Premetamorphic larvae excreted over 50% of their nitrogen waste as urea and the balance as ammonia.

A further characterization of the cinnamon gene in Drosophila melanogaster

The X-linked, xanthine dehydrogenase (XDH) deficient cinnamon (cin, 1-0.0) eye color mutant of Drosophila melanogaster is a female sterile and as a result, cannot be maintained as a homozygous stock. Since the eye color of cin progeny from heterozygous females is maternally affected, genotypically cin flies have a wild type eye color. Supplementation of the culture medium with 0.02% allopurinol (4-hydroxypyrazolo (3,4-d), pyrimidine) (an XDH inhibitor) causes maternally affected cin flies to express a fully mutant eye color while it has no effect on the eye color of wild type flies. Using an allopurinol screening system we successfully induced two new alleles cin3 and cin4 with ethyl methane sulfonate (EMS). cin3 is more severe than cin4 and cin with respect to three cin phenotypes suggesting that cin and cin4 are leaky. cin3 mutants have no greater levels of XDH throughout development than do maternally affected ma-l flies while cin and cin4 have higher XDH levels as late as the 96 h pupa. Using overlapping deficiencies and duplications, an unequivocal order of genes mapping at the tip of the X-chromosome (1-0.0) was obtained: l(1)J1, cin, arth, y, ac, sc and svr. Gynandromorphs marked with cin and y were employed to demonstrate that the action of cin+ is non-autonomous. A selection scheme using a combination of allopurinol and purine which renders cin flies conditionally lethal is described.

Coordinate regulation of purine nucleoside phosphorylase and xanthine dehydrogenase levels in chick liver

Previously it has been shown that the levels of xanthine dehydrogenase in chick liver can be increased by feeding high-protein diets, adenine, and allopurinol (a xanthine dehydrogenase inhibitor). Also, it has been shown that starvation increases the level of xanthine dehydrogenase in chick liver and that unsaturated fatty acids in the diet suppress the levels of xanthine dehydrogenase in the liver. Results reported here show that starvation and high-protein diets enhance the levels of purine nucleoside phosphorylase and that unsaturated fatty acids suppress the level of this enzyme. In contrast with xanthine dehydrogenase, adenine and allopurinol have no effect on purine nucleoside phosphorylase levels. These results suggest that dietary protein and unsaturated fatty acids regulate more than one enzyme involved in the production of uric acid. Levels of xanthine dehydrogenase in the pancreas can be increased by feeding and decreased by starvation or feeding unsaturated fatty acids. None of these procedures has any effect on the level of pancreatic purine nucleoside phosphorylase.

Regulation of xanthine dehydrogenase levels in liver and pancreas of the chick

Xanthine dehydrogenase activity in the liver and pancreas of the chick has been shown to flactuate upon starvation and refeeding. Using combined isotope labeling an immunochemical approaches, a study has been made of the rates of synthesis and degradation of bulk soluble protein and xanthine dehydrogenase in both of these tissues. The increase in liver xanthine dehadrogenasee specific activity during starvation is due to the decrease in size of the organ with no change in the total rate of enzyme synthesis in the organ. The decrease in pancreatic xanthine dehydrogenase activity during starvation is due to a decrease in its rate of synthesis. Also, it was found that the degradation rate of bulk soluble protein in the pancreas increases during starvation. The overshoot in pancreatic xanthine dehydrogenase activity observed on refeeding appears to be due to a rapid return of xanthine dehydrogenase synthesis to normal with a slower return to normal in the rates of soluble protein degradation and synthesis.

Suppression of chick pancreatic xanthine dehydrogenase by unsaturated fatty acids

A study of pancreatic xanthine dehydrogenase levels in chicks immediately after hatching has revealed that the sharp developmental increase normally occurring can be suppressed by maintenance on whole egg ( Fisher et al., 1967; Woodward and Fisher, 1967 ). Further work has shown that ether extracts of egg yolks are equally effective in supressing this developmental increase. Of the lipid components present, four have been found to affect the accumulation of pancreatic xanthine dehydrogenase: linolenic, linoleic, and oleic acids suppress and stearic acid enhances. It seems reasonable to believe that the suppressing activity of ether extracts of eggs is due to the presence of unsaturated fatty acids. The administration of specific fatty acids leads to increased concentrations of these materials in the lipids of the pancreas.