DOCSLIB.ORG

Alternative Pathways of Glucose Metabolism II. Nucleotides from The

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Alternative Pathways of Glucose Metabolism II. Nucleotides from The Alternative Pathways of Glucose Metabolism II . Nucleotides from the Acid-soluble Fraction of Normal and Tumor Tissues and Studies on Nucleic Acid Synthesis in Tumors*t HANNS SCHMITZ4 VAN R. POTTER, ROBERT B. HTJRLBERT,@ AND DWAIN M. WHITE (McArdie Memovial Laboratory, the Medical School, University of Wisconain, Madison, WI..) The first paper (18) in this series on the alterna MATERIALS AND METHODS tive pathways of glucose metabolism established The present study has involved the measure the fact that radioactivity from glucose-i-C'4 was ment of the specific activities of the free 5' mono-, readily incorporated into the pentose moiety of the di-, and triphosphates of adenosine, guanosine, ribonucleic and desoxyribonucleic acids of Flexner cytidine, and uridine from the acid-soluble extract Jobling tumors in rats, and described the over-all of tumor tissue in relation to the specific activities distribution of radioactivity in the acid-soluble of the corresponding nucleotides that were oh and acid-insoluble fractions of tumor and liver tis tamed by chemical or enzymatic hydrolysis of the sue at various time periods. The acid-soluble frac nucleic acids from the same tissue samples, at tion of tissue contains an appreciable amount of specified time intervals after the injection of glu free nucleotides which are possible intermediary cose-1-C'4. The experimental plan corresponds compounds in the synthesis of the nucleic acids exactly to that described in the preceding paper; (6, 7, 8, 9, 13, 16). It was noted (18) that as the C'4 many of the radioactive samples that were used for disappeared from the acid-soluble fraction, the the over-all survey (18) were also used for the de nucleic acids of the acid-insoluble residue showed tailed study reported here, and the plating and the increases in radioactivity, but it was evident that counting procedures were the same.' only by the isolation of the individual nucleotides Chromatography of acid-solublefractions.—The acid-soluble in pure form could any information on nucleic acid extracts were prepared as previously described (18), and the synthesis from the possible intermediates be ob PCA2 extract was used for chromatography without previous tained. This task was greatly facilitated by con fractionation with barium or other procedures. The chromatog raphy was usually carried out by means of the mechanically comitant studies in this laboratory in which operated two-column system of anion exchange with Dower-i Cohn's methods (4) for nucleotide separations in the formate form in both columns, and with a device for have been adapted to the study of unknown mix automatically changing the concentration of eluant (9). The tures (9), and in which the isolation of a number of two columns employed are referred to as the formic acid sys tem and the ammonium formate system or as the type I and hitherto unrecognized nucleotides has been ac type II systems, respectively. They are described fully else complished (16). where (9). In using the two columns, selected fractions from the formic acid system were pooled and rechromatographed S A preliminary report has appeared (17). t This workwassupportedinpartby a grant(No.C-646) ‘Much of the plating and counting was done by Mrs. from the National Cancer Institute, National Institutes of Dorothy McManus and Mrs. Edith Wallestad under the Health, United States Public Health Service, and in part by general supervision of Dr. Charles Heidelberger of this de an institutional grant (No. 71) from the American Cancer partment. This skilled assistance is gratefully acknowledged. Society. Throughout this paper “c.p.m.―willbe used to mean counts @ Present address: Institut für expenimentelle Krebs per minute in the internal gas flowproportional counters used forschung, UniversitätHeidelberg. in this study. §Present address: Kemiska Institutionen, Karolinska S Abbreviations are as follows: PCA, perchioric acid; RNA, Institutet, Stockholm. nibonucleic acid; DNA, desoxynibonucleic acid; MP, mono phosphate; DP, diphosphate; TP, triphosphate; A, adenosine; Received for publication September 9, 1953. G, guanosine; I, inosine; C, cytidine; U, uridine. 66 Downloaded from cancerres.aacrjournals.org on September 25, 2021. © 1954 American Association for Cancer Research. SCHMITZ et al.—Alternative Pathways of Glucose Metabolism. II 67 on the ammonium formate system to increase the purity of than one nucleotide, and this heterogeneity is individual nucleotides before determining their radioactivity. noted on the chart on the basis of the results oh In the present work, the longer columns (1X20 cm.) were em ployed in combination with a 500-ml. mixing flask. This pro tamed by rechromatographing these peaks on the cedure improves the resolution obtained with the formic acid type II columns insofar as the components have column and yields less heterogenous fractions for rechro been identified. The complexity of the fractions of matography on the type II column. a given tissue extract is of course much greater As a preface to the extensive fractionation of the radio than is indicated in Chart 1, since this chromato active samples, the nature of the nucleotide mixture in the acid-soluble fraction of Flexner-Jobling rat carcinoma was gram gives no information about the compounds compared to that of several nontumor tissues, by means of that do not absorb ultraviolet light. It is evident, the formicacid system. however, from this chart that the tumor contains Nudeotid.. o@ained from nucleic acids.—The mononucleo a large number of different nucleotides, many of tides of the RNA2 were obtained by treating the mixed sodium nucleates (7) with 0.1 M NaOH (1.0 ml/iO mg) for 20—24 which have not been reported in tumor or in non hours at 88 C. to hydrolyze the RNA. The DNA was then pre tumor tissues prior to the present studies (16). cipitated by making the solution 0.1N with respect to HC1, For this reason it was important to note whether and the supernatant containingthe RNA nucleotideswas neu the nucleotide .pattern shown in Chart 1 was tralized and placed on the type I columns (TX1O cm. with unique for tumor, or for growing or actively syn 250-mi. mixing flask). Since this mixture of nueleotides is much simpler than that of the acid-soluble fractions, re thesizing tissues, and, accordingly, two nongrow chromatography was unnecessary. The precipitated DNA was ing tissues in addition to liver have been included @ washed with 0.01 N HC1, reprocessed several times with 0.1 N for comparison with the tumor. Chart represents NaOH at 800C. for 20 minutes, reprecipitated with HC1 a chromatogram for liver, while the results for each time as before, and finally washed with alcohol and dried. The mononucleotidesfrom the DNA were obtained by en brain and muscle are shown in Charts 3 and 4, re. zymatic hydrolysis with a combination of desoxyribonuclease' spectively. All these tissues were from tumor (14) and a phosphodiesterase (10, ii) obtained from snake bearing rats. venom.4 The latter enzyme was not entirely free from phos These chromatograms will not be described in phomonoesterase, since the ion exchange chromatograms detail, since their features are evident by inspec yielded a relatively large amount of nucleosides. The incuba tion mixtures were extracted with cold PCA at a final con tion. However, it may be noted that the nucleotide centration of 0.4 N, the perchlorate was precipitated as the pattern for liver from tumor-bearing rats shown in @ potassium salt, and the supernatant fluid at pH 6.8 was placed Chart is quite similar to that for normal liver (9) on type I columns that were identical with those used for the and that in both cases there is a significant peak RNA hydrolysates. The sample effluents as well as the water wash (200 ml.) was collected in 8-ml. fractions. These frac (labeled ADP-X on Chart @)that does not appear tions contained the nucleosides as well as a portion of all four in the chromatograms or rechromatograms for tu of the bases. Suitable fractions containing the nucleosides mor, brain, or skeletal muscle. This peak contains were then subjected to paper chromatography according to one or more derivatives of an adenosine polyphos Carter (8) with the use of the disodium phosphate isoamyl phate that are as yet not fully identified (9). The alcohol solventsystem.' Specific activities were calculated from radioactivity measurements on individual nucleosides or chromatograms for brain and tumor are quite sim nucleotides depending on the quantity available. ilar and resemble each other more than they re Identification of nucleotides.—The identification of the semble liver or muscle. Both apparently lack the individual nucleotides that were chromatographically sepa ADP-Xpeakthat is foundin liver,andbothpos rated was made on the basis of their positions on the type I and type U columns, their ultraviolet absorption spectra in sess the UDP derivatives that are not seen in the acid and in alkali, their content of total and acid-labile phos muscle chromatogram, which also lacks ADP-X. phorus, their apparent nibosecontent by the orcinolmethod, Since brain is certainly not a growing tissue, at the and other tests, all of which are adequately described else present there appears to be no correlation with where (9,16). growth processes insofar as these nucleotide pat RESULTS terns per se are concerned. However, the turnover Di4,tribzdion of free nucleoti4&, in acid-soluble of the nucleotides shown in these chromatograms extracta.—Chart 1 shows an ion exchange chro may be greatly different, as the isotopic studies in matogram of the acid-soluble extract of Flexuer the second section of this report will show. Jobling rat carcinoma as obtained from a formic Although not shown in Chart @,the livers from acid column.
Load more

Recommended publications
  • 35 Disorders of Purine and Pyrimidine Metabolism
    35 Disorders of Purine and Pyrimidine Metabolism Georges van den Berghe, M.- Françoise Vincent, Sandrine Marie 35.1 Inborn Errors of Purine Metabolism – 435 35.1.1 Phosphoribosyl Pyrophosphate Synthetase Superactivity – 435 35.1.2 Adenylosuccinase Deficiency – 436 35.1.3 AICA-Ribosiduria – 437 35.1.4 Muscle AMP Deaminase Deficiency – 437 35.1.5 Adenosine Deaminase Deficiency – 438 35.1.6 Adenosine Deaminase Superactivity – 439 35.1.7 Purine Nucleoside Phosphorylase Deficiency – 440 35.1.8 Xanthine Oxidase Deficiency – 440 35.1.9 Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency – 441 35.1.10 Adenine Phosphoribosyltransferase Deficiency – 442 35.1.11 Deoxyguanosine Kinase Deficiency – 442 35.2 Inborn Errors of Pyrimidine Metabolism – 445 35.2.1 UMP Synthase Deficiency (Hereditary Orotic Aciduria) – 445 35.2.2 Dihydropyrimidine Dehydrogenase Deficiency – 445 35.2.3 Dihydropyrimidinase Deficiency – 446 35.2.4 Ureidopropionase Deficiency – 446 35.2.5 Pyrimidine 5’-Nucleotidase Deficiency – 446 35.2.6 Cytosolic 5’-Nucleotidase Superactivity – 447 35.2.7 Thymidine Phosphorylase Deficiency – 447 35.2.8 Thymidine Kinase Deficiency – 447 References – 447 434 Chapter 35 · Disorders of Purine and Pyrimidine Metabolism Purine Metabolism Purine nucleotides are essential cellular constituents 4 The catabolic pathway starts from GMP, IMP and which intervene in energy transfer, metabolic regula- AMP, and produces uric acid, a poorly soluble tion, and synthesis of DNA and RNA. Purine metabo- compound, which tends to crystallize once its lism can be divided into three pathways: plasma concentration surpasses 6.5–7 mg/dl (0.38– 4 The biosynthetic pathway, often termed de novo, 0.47 mmol/l). starts with the formation of phosphoribosyl pyro- 4 The salvage pathway utilizes the purine bases, gua- phosphate (PRPP) and leads to the synthesis of nine, hypoxanthine and adenine, which are pro- inosine monophosphate (IMP).
    [Show full text]
  • Pro-Aging Effects of Xanthine Oxidoreductase Products
    antioxidants Review Pro-Aging Effects of Xanthine Oxidoreductase Products , , Maria Giulia Battelli y , Massimo Bortolotti y , Andrea Bolognesi * z and Letizia Polito * z Department of Experimental, Diagnostic and Specialty Medicine-DIMES, Alma Mater Studiorum, University of Bologna, Via San Giacomo 14, 40126 Bologna, Italy; [email protected] (M.G.B.); [email protected] (M.B.) * Correspondence: [email protected] (A.B.); [email protected] (L.P.); Tel.: +39-051-20-9-4707 (A.B.); +39-051-20-9-4729 (L.P.) These authors contributed equally. y Co-last authors. z Received: 22 July 2020; Accepted: 4 September 2020; Published: 8 September 2020 Abstract: The senescence process is the result of a series of factors that start from the genetic constitution interacting with epigenetic modifications induced by endogenous and environmental causes and that lead to a progressive deterioration at the cellular and functional levels. One of the main causes of aging is oxidative stress deriving from the imbalance between the production of reactive oxygen (ROS) and nitrogen (RNS) species and their scavenging through antioxidants. Xanthine oxidoreductase (XOR) activities produce uric acid, as well as reactive oxygen and nitrogen species, which all may be relevant to such equilibrium. This review analyzes XOR activity through in vitro experiments, animal studies and clinical reports, which highlight the pro-aging effects of XOR products. However, XOR activity contributes to a regular level of ROS and RNS, which appears essential for the proper functioning of many physiological pathways. This discourages the use of therapies with XOR inhibitors, unless symptomatic hyperuricemia is present.
    [Show full text]
  • Thermostable and Long-Circulating Albumin-Conjugated Arthrobacter Globiformis Urate Oxidase
    pharmaceutics Article Thermostable and Long-Circulating Albumin-Conjugated Arthrobacter globiformis Urate Oxidase Byungseop Yang and Inchan Kwon * School of Materials Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Korea; [email protected] * Correspondence: [email protected]; Tel.: +82-62-715-2312 Abstract: Urate oxidase derived from Aspergillus flavus has been investigated as a treatment for tumor lysis syndrome, hyperuricemia, and gout. However, its long-term use is limited owing to potential immunogenicity, low thermostability, and short circulation time in vivo. Recently, urate oxidase isolated from Arthrobacter globiformis (AgUox) has been reported to be thermostable and less immunogenic than the Aspergillus-derived urate oxidase. Conjugation of human serum albumin (HSA) to therapeutic proteins has become a promising strategy to prolong circulation time in vivo. To develop a thermostable and long-circulating urate oxidase, we investigated the site-specific conjugation of HSA to AgUox based on site-specific incorporation of a clickable non-natural amino acid (frTet) and an inverse electron demand Diels–Alder reaction. We selected 14 sites for frTet incorporation using the ROSETTA design, a computational stability prediction program, among which AgUox containing frTet at position 196 (Ag12) exhibited enzymatic activity and thermostability comparable to those of wild-type AgUox. Furthermore, Ag12 exhibited a high HSA conjugation yield without compromising the enzymatic activity, generating well-defined HSA-conjugated AgUox (Ag12-HSA). In mice, the serum half-life of Ag12-HSA was approximately 29 h, which was roughly Citation: Yang, B.; Kwon, I. 17-fold longer than that of wild-type AgUox. Altogether, this novel formulated AgUox may hold Thermostable and Long-Circulating enhanced therapeutic efficacy for several diseases.
    [Show full text]
  • Mechanisms of Synthesis of Purine Nucleotides in Heart Muscle Extracts
    Mechanisms of Synthesis of Purine Nucleotides in Heart Muscle Extracts David A. Goldthwait J Clin Invest. 1957;36(11):1572-1578. https://doi.org/10.1172/JCI103555. Research Article Find the latest version: https://jci.me/103555/pdf MECHANISMS OF SYNTHESIS OF PURINE NUCLEOTIDES IN HEART MUSCLE EXTRACTS1 BY DAVID A. GOLDTHWAIT2 (From the Departments of Biochemistry and Medicine, Western Reserve University, Cleveland, Ohio) (Submitted for publication February 18, 1957; accepted July 18, 1957) The key role of ATP, a purine nucleotide, in 4. Adenine or Hypoxanthine + PRPP -> AMP the conversion of chemical energy into mechanical or Inosinic Acid (IMP) + P-P. work by myocardial tissue is well established (1, The third mechanism of synthesis is through the 2). The requirement for purine nucleotides has phosphorylation of a purine nucleoside (8, 9): also been demonstrated in the multiple synthetic 5. Adenosine + ATP -, AMP + ADP. reactions which maintain all animal cells in the Several enzymatic mechanisms are known which steady state. Since the question immediately arises result in the degradation of purine nucleotides and whether the purine nucleotides are themselves in nucleosides. The deamination of adenylic acid is a steady state, in which their rates of synthesis well known (10): equal their rates of degradation, it seems reason- 6. AMP -* IMP + NH8. able to investigate first what mechanisms of syn- Non-specific phosphatases (11) as well as spe- thesis and degradation may be operative. cific 5'-nucleotidases (12) have been described At present, there are three known pathways for which result in dephosphorylation: the synthesis of purine nucleotides. The first is 7.
    [Show full text]
  • Calcium 5'-Ribonucleotides
    CALCIUM 5'-RIBONUCLEOTIDES Prepared at the 18th JECFA (1974), published in NMRS 54B (1975) and in FNP 52 (1992). Metals and arsenic specifications revised at the 57th JECFA (2001). An ADI ‘not specified’ was established at the 18th JECFA (1974). SYNONYMS Calcium ribonucleotides, INS No. 634 DEFINITION Chemical names (Mixture of) calcium inosine-5'-monophosphate and calcium guanosine-5'- monophosphate Chemical formula C10H11CaN4O8P · x H2O and C10H12CaN5O8P · x H2O Structural formula Calcium 5’-guanylate Calcium 5’-inosinate Assay Not less than 97% and not more than the equivalent of 102% of C10H11CaN4O8P and C10H12CaN5O8P, calculated on the anhydrous basis. The proportion of C10H11CaN4O8P or C10H12CaN5O8P to the sum of them is between 47% and 53%. DESCRIPTION Odourless, white or off-white crystals or powder FUNCTIONAL USES Flavour enhancer CHARACTERISTICS IDENTIFICATION Solubility (Vol. 4) Sparingly soluble in water Test for ribose (Vol. 4) Passes test Test for organic phosphate Passes test (Vol. 4) Test 5 ml of a 1 in 2,000 solution Test for inosinic acid To 2 ml of a 1 in 2,000 solution add 2 ml of 10% hydrochloric acid and 0.1 g of zinc powder, heat in a water bath for 10 min, and filter. Cool the filtrate in ice water, add 1 ml of a 3 in 1,000 sodium nitrite solution, shake well, and allow to stand for 10 min. Add 1 ml of a 1 in 200 ammonium sulfamate solution, shake well, and allow to stand for 5 min. Add 1 ml of a 1 in 500 N-(1- naphthyl)-ethylenediamine dihydrochloride solution.
    [Show full text]
  • Effects of Allopurinol and Oxipurinol on Purine Synthesis in Cultured Human Cells
    Effects of allopurinol and oxipurinol on purine synthesis in cultured human cells William N. Kelley, James B. Wyngaarden J Clin Invest. 1970;49(3):602-609. https://doi.org/10.1172/JCI106271. Research Article In the present study we have examined the effects of allopurinol and oxipurinol on thed e novo synthesis of purines in cultured human fibroblasts. Allopurinol inhibits de novo purine synthesis in the absence of xanthine oxidase. Inhibition at lower concentrations of the drug requires the presence of hypoxanthine-guanine phosphoribosyltransferase as it does in vivo. Although this suggests that the inhibitory effect of allopurinol at least at the lower concentrations tested is a consequence of its conversion to the ribonucleotide form in human cells, the nucleotide derivative could not be demonstrated. Several possible indirect consequences of such a conversion were also sought. There was no evidence that allopurinol was further utilized in the synthesis of nucleic acids in these cultured human cells and no effect of either allopurinol or oxipurinol on the long-term survival of human cells in vitro could be demonstrated. At higher concentrations, both allopurinol and oxipurinol inhibit the early steps ofd e novo purine synthesis in the absence of either xanthine oxidase or hypoxanthine-guanine phosphoribosyltransferase. This indicates that at higher drug concentrations, inhibition is occurring by some mechanism other than those previously postulated. Find the latest version: https://jci.me/106271/pdf Effects of Allopurinol and Oxipurinol on Purine Synthesis in Cultured Human Cells WILLIAM N. KELLEY and JAMES B. WYNGAARDEN From the Division of Metabolic and Genetic Diseases, Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, North Carolina 27706 A B S TR A C T In the present study we have examined the de novo synthesis of purines in many patients.
    [Show full text]
  • Mechanism of Excessive Purine Biosynthesis in Hypoxanthine- Guanine Phosphoribosyltransferase Deficiency
    Mechanism of excessive purine biosynthesis in hypoxanthine- guanine phosphoribosyltransferase deficiency Leif B. Sorensen J Clin Invest. 1970;49(5):968-978. https://doi.org/10.1172/JCI106316. Research Article Certain gouty subjects with excessive de novo purine synthesis are deficient in hypoxanthineguanine phosphoribosyltransferase (HG-PRTase [EC 2.4.2.8]). The mechanism of accelerated uric acid formation in these patients was explored by measuring the incorporation of glycine-14C into various urinary purine bases of normal and enzyme-deficient subjects during treatment with the xanthine oxidase inhibitor, allopurinol. In the presence of normal HG-PRTase activity, allopurinol reduced purine biosynthesis as demonstrated by diminished excretion of total urinary purine or by reduction of glycine-14C incorporation into hypoxanthine, xanthine, and uric acid to less than one-half of control values. A boy with the Lesch-Nyhan syndrome was resistant to this effect of allopurinol while a patient with 12.5% of normal enzyme activity had an equivocal response. Three patients with normal HG-PRTase activity had a mean molar ratio of hypoxanthine to xanthine in the urine of 0.28, whereas two subjects who were deficient in HG-PRTase had reversal of this ratio (1.01 and 1.04). The patterns of 14C-labeling observed in HG-PRTase deficiency reflected the role of hypoxanthine as precursor of xanthine. The data indicate that excessive uric acid in HG-PRTase deficiency is derived from hypoxanthine which is insufficiently reutilized and, as a consequence thereof, catabolized inordinately to uric acid. The data provide evidence for cyclic interconversion of adenine and hypoxanthine derivatives. Cleavage of inosinic acid to hypoxanthine via inosine does […] Find the latest version: https://jci.me/106316/pdf Mechanism of Excessive Purine Biosynthesis in Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency LEIF B.
    [Show full text]
  • Low Uric Acid Diet Diet FAQ's What Is Uricvs Acid? Uric Acid Is a Byproduct of Purines (PYUR-Eenz)
    o ?? ou need t Y our reduce y Uric Acid! Understanding the Low Uric Acid Diet Diet FAQ's What is Uricvs Acid? Uric acid is a byproduct of purines (PYUR-eenz). Purines are naturally occurring substances and are found in many food items. As purines are broken down in the body, they are eliminated as uric acid. What does Uric Acid have to do with CKD? Normally, uric acid passes through the kidneys and is excreted in urine. However, when the kidneys cannot process all of the uric acid, hyperuricemia, or elevated uric acid in the blood, may develop. Recent research has determined that approximately 10% of Americans with Chronic Kidney Disease (CKD) also have gout, and if left untreated, can further worsen kidney function. Why do I need a diet that reduces Uric Acid? When your kidneys are not functioning properly, they do not filter out uric acid properly, thus potentially leading to a number of health issues. Elevated hyperuricemia (elevated uric acid levels) may cause: • Worsening of kidney function • Flare up of gout • Damage to affected joints Diet Do's and Don'ts Do Don't DO Don't Do Don't Exercise: even 1 minute of moderate to brisk Don’t take baker’s yeast or brewer’s yeast as a walking is helpful supplement Drink 8-12 cups o f fluid daily, this may help reduce Don't drink ( or try to limit) alcohol. Alcohol increases kidney stone formation and decrease uric acid purine production, thus further worsening crystals hyperuricemia Foods to limit Limit meat to 3 ounces per meal Limit high fat foods, such as salad dressings, ice cream, fried foods, & gravies.
    [Show full text]
  • Study of Purine Metabolism in a Xanthinuric Female
    Study of Purine Metabolism in a Xanthinuric Female MICHAEL J. BRADFORD, IRWIN H. KRAKOFF, ROBERT LEEPER, and M. EARL BALis From the Sloan-Kettering Institute, Sloan-Kettering Division of Cornell University Graduate School of Medical Sciences, and the Department of Medicine of Memorial and James Ewing Hospitals, New York 10021 A B S TR A C T A case of xanthinuria is briefly de- Case report in brief. The patient is a 62 yr old scribed, and the results of in vivo studies with Puerto Rican grandmother, whose illness is de- 4C-labeled oxypurines are discussed. The data scribed in detail elsewhere.' Except for mild pso- demonstrate that the rate of the turnover of uric riasis present for 30 yr, she has been in good acid is normal, despite an extremely small uric health. On 26 June 1966, the patient was admitted acid pool. Xanthine and hypoxanthine pools were to the Second (Cornell) Medical Service, Bellevue measured and their metabolism evaluated. The Hospital, with a 3 day history of pain in the right bulk of the daily pool of 276 mg of xanthine, but foot and fever. The admission physical examina- only 6% of the 960 mg of hypoxanthine, is ex- tion confirmed the presence of monoarticular ar- creted. Thus, xanthine appears to be a metabolic thritis and mild psoriasis. The patient's course in end product, whereas hypoxanthine is an active the hospital was characterized by recurrent fevers intermediate. Biochemical implications of this find- to 104°F and migratory polyarthritis, affecting ing are discussed. both ankles, knees, elbows, wrists, and hands over a 6 wk period.
    [Show full text]
  • Shaping Rolling Circle Amplification Products Into DNA Nanoparticles by Incorporation of Modified Nucleotides and Their Applicat
    molecules Communication Shaping Rolling Circle Amplification Products into DNA Nanoparticles by Incorporation of Modified Nucleotides and Their Application to In Vitro and In Vivo Delivery of a Photosensitizer Kyoung-Ran Kim 1, Pascal Röthlisberger 2, Seong Jae Kang 1, Kihwan Nam 3, Sangyoup Lee 3, Marcel Hollenstein 2 ID and Dae-Ro Ahn 1,4,* ID 1 Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Korea; [email protected] (K.-R.K.); [email protected] (S.J.K.) 2 Department of Structural Biology and Chemistry, Laboratory for Bioorganic Chemistry of Nucleic Acids, Institut Pasteur, CNRS UMR3523, 28, rue du Docteur Roux, 75724 Paris CEDEX 15, France; [email protected] (P.R.); [email protected] (M.H.) 3 Center for Bionics, Biomedical Research Institute, Korea Institute of Science and Technology (KIST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Korea; [email protected] (K.N.); [email protected] (S.L.) 4 Division of Biomedical Science and Technology, KIST School, Korea University of Science and Technology (UST), Hwarangno 14-gil 5, Seongbuk-gu, Seoul 02792, Korea * Correspondence: [email protected] Academic Editor: Shigeki Sasaki Received: 10 June 2018; Accepted: 20 July 2018; Published: 23 July 2018 Abstract: Rolling circle amplification (RCA) is a robust way to generate DNA constructs, which are promising materials for biomedical applications including drug delivery because of their high biocompatibility. To be employed as a drug delivery platform, however, the DNA materials produced by RCA need to be shaped into nanoparticles that display both high cellular uptake efficiency and nuclease resistance.
    [Show full text]
  • Purine and Pyrimidine Metabolism in Human Epidermis* Jean De Bersaques, Md
    THE JOURNAL OP INVESTIGATIVE DERMATOLOGY Vol. 4s, No. Z Copyright 1957 by The Williams & Wilkins Co. Fri nte,1 in U.S.A. PURINE AND PYRIMIDINE METABOLISM IN HUMAN EPIDERMIS* JEAN DE BERSAQUES, MD. The continuous cellular renewal occurring inthine, which contained 5% impurity, and for uric the epidermis requires a very active synthesisacid, which consisted of 3 main components. The reaction was stopped after 1—2 hours in- and breakdown of nuclear and cytoplasmiecubation at 37° and the products were spotted on nucleic acids. Data on the enzyme systemsWhatman 1 filter paper sheets. According to the participating in these metabolic processes arereaction products expected, a choice was made of rather fragmentary (1—9) and some are, inat least 2 among the following solvents, all used terms of biochemical time, in need of up- in ascending direction: 1. isoamyl alcohol—5% Na2HPO4 (1:1), dating. In some other publications (10—18), 2. water-saturated n-butanol, the presence and concentration of various in- 3. distilled water, termediate products is given. 4. 80% formic acid—n-hutanol——n-propanol— In this paper, we tried to collect and supple- acetone—30% trichloro-aeetic acid (5:8:4: ment these data by investigating the presence 5:3), 5. n-butanol——4% boric acid (43:7), or absence in epidermis of enzyme systems 6. isobutyrie acid—water—ammonia 0.880—ver- that have been described in other tissues. sene 0.1M(500:279:21:8), This first investigation was a qualitative one, 7. upper phase of ethyl acetate—water—formic and some limitations were set by practical acid (12:7:1), 8.
    [Show full text]
  • Hypoxanthine, Xanthine, and Uric Acid Concentrations in Plasma
    003 1 -3998/93/3406-0767$03.00/0 PEDIATRIC RESEARCH Vol. 34, No. 6, 1993 Copyright O 1993 International Pediatric Research Foundation, Inc. Printed in U.S. A. Hypoxanthine, Xanthine, and Uric Acid Concentrations in Plasma, Cerebrospinal Fluid, Vitreous Humor, and Urine in Piglets Subjected to Intermittent Versus Continuous Hypoxemia LAURITZ STOLTENBERG, TERJE ROOTWELT, STEPHANIE BYASAETER, TORLEIV 0. ROGNUM, AND OLA D. SAUGSTAD Department of Pediatric Research [L.S.. T.R..S.0.. O.D.S.].Institute ofSurgica1 Research [L.S.. T.R.],and Insritute of Forensic Medicine [L.S., T.O.R.],The National Hospital, 0027 Oslo 1, Norway ABSTRACT. Infants with sudden infant death syndrome compared with 20% in infants that die suddenly or unexpectedly have higher hypoxanthine (Hx) concentrations in their from other causes (4). It was concluded in this study that SIDS, vitreous humor than infants with respiratory distress syn- in most cases, is probably not a sudden event but may be drome and other infant control populations. However, pre- preceded by a relatively long period of respiratory failure and vious research on piglets and pigs applying continuous hypoxia. However, previous experiments on piglets applying hypoxemia has not been able to reproduce the concentra- different degrees and durations of CH have not been able to tions observed in infants with sudden infant death syn- reproduce equally high vitreous humor Hx values as observed in drome. To test whether intermittent hypoxemia could, in SIDS (5). Perhaps the higher Hx concentration formed in vitre- part, explain this observed difference, Hx, xanthine (X), ous humor of SIDS victims is due to the fact that these infants and uric acid were measured in vitreous humor, urine, suffer repeated episodes of hypoxemia before they die.
    [Show full text]