Availability and Quality of Published Data on the Purine Content of Foods, ⋆ T Alcoholic Beverages, and Dietary Supplements ⁎ Beiwen Wua, , Janet M
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REDUCTION of PURINE CONTENT in COMMONLY CONSUMED MEAT PRODUCTS THROUGH RINSING and COOKING by Anna Ellington (Under the Directio
REDUCTION OF PURINE CONTENT IN COMMONLY CONSUMED MEAT PRODUCTS THROUGH RINSING AND COOKING by Anna Ellington (Under the direction of Yen-Con Hung) Abstract The commonly consumed meat products ground beef, ground turkey, and bacon were analyzed for purine content before and after a rinsing treatment. The rinsing treatment involved rinsing the meat samples using a wrist shaker in 5:1 ratio water: sample for 2 or 5 minutes then draining or centrifuging to remove water. The total purine content of 25% fat ground beef significantly decreased (p<0.05) from 8.58 mg/g protein to a range of 5.17-7.26 mg/g protein after rinsing treatments. After rinsing and cooking an even greater decrease was seen ranging from 4.59-6.32 mg/g protein. The total purine content of 7% fat ground beef significantly decreased from 7.80 mg/g protein to a range of 5.07-5.59 mg/g protein after rinsing treatments. A greater reduction was seen after rinsing and cooking in the range of 4.38-5.52 mg/g protein. Ground turkey samples showed no significant changes after rinsing, but significant decreases were seen after rinsing and cooking. Bacon samples showed significant decreases from 6.06 mg/g protein to 4.72 and 4.49 after 2 and 5 minute rinsing and to 4.53 and 4.68 mg/g protein after 2 and 5 minute rinsing and cooking. Overall, this study showed that rinsing foods in water effectively reduces total purine content and subsequent cooking after rinsing results in an even greater reduction of total purine content. -
Chapter 23 Nucleic Acids
7-9/99 Neuman Chapter 23 Chapter 23 Nucleic Acids from Organic Chemistry by Robert C. Neuman, Jr. Professor of Chemistry, emeritus University of California, Riverside [email protected] <http://web.chem.ucsb.edu/~neuman/orgchembyneuman/> Chapter Outline of the Book ************************************************************************************** I. Foundations 1. Organic Molecules and Chemical Bonding 2. Alkanes and Cycloalkanes 3. Haloalkanes, Alcohols, Ethers, and Amines 4. Stereochemistry 5. Organic Spectrometry II. Reactions, Mechanisms, Multiple Bonds 6. Organic Reactions *(Not yet Posted) 7. Reactions of Haloalkanes, Alcohols, and Amines. Nucleophilic Substitution 8. Alkenes and Alkynes 9. Formation of Alkenes and Alkynes. Elimination Reactions 10. Alkenes and Alkynes. Addition Reactions 11. Free Radical Addition and Substitution Reactions III. Conjugation, Electronic Effects, Carbonyl Groups 12. Conjugated and Aromatic Molecules 13. Carbonyl Compounds. Ketones, Aldehydes, and Carboxylic Acids 14. Substituent Effects 15. Carbonyl Compounds. Esters, Amides, and Related Molecules IV. Carbonyl and Pericyclic Reactions and Mechanisms 16. Carbonyl Compounds. Addition and Substitution Reactions 17. Oxidation and Reduction Reactions 18. Reactions of Enolate Ions and Enols 19. Cyclization and Pericyclic Reactions *(Not yet Posted) V. Bioorganic Compounds 20. Carbohydrates 21. Lipids 22. Peptides, Proteins, and α−Amino Acids 23. Nucleic Acids ************************************************************************************** -
Human Hypoxanthine (Guanine) Phosphoribosyltransferase: An
Proc. NatL Acad. Sci. USA Vol. 80, pp. 870-873, Febriary 1983 Medical Sciences Human hypoxanthine (guanine) phosphoribosyltransferase: An amino acid substitution in a mutant form of the enzyme isolated from a patient with gout (reverse-phase HPLC/peptide mapping/mutant enzyme) JAMES M. WILSON*t, GEORGE E. TARRt, AND WILLIAM N. KELLEY*t Departments of *Internal Medicine and tBiological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109 Communicated by James B. Wyngaarden, November 3, 1982 ABSTRACT We have investigated the molecular basis for a tration ofenzyme protein. in both erythrocytes (3) and lympho- deficiency ofthe enzyme hypoxanthine (guanine) phosphoribosyl- blasts (4); (ii) a normal Vm., a normal Km for 5-phosphoribosyl- transferase (HPRT; IMP:pyrophosphate-phosphoribosyltransfer- 1-pyrophosphate, and a 5-fold increased Km for hypoxanthine ase, EC 2.4.2.8) in a patient with a severe form of gout. We re-. (unpublished data); (iii) a normal isoelectric point (3, 4) and ported in previous studies the isolation of a unique structural migration during nondenaturing polyacrylamide gel electro- variant of HPRT from this patient's erythrocytes and cultured phoresis (4); and (iv) -an apparently smaller subunit molecular lymphoblasts. This enzyme variant, which is called HPRTOnd0., weight as evidenced by an increased mobility during Na- is characterized by a decreased concentration of HPRT protein DodSO4/polyacrylamide gel electrophoresis (3, 4). in erythrocytes and lymphoblasts, a normal Vm.., a 5-fold in- Our study ofthe tryptic peptides and amino acid composition creased Km for hypoxanthine, a normal isoelectric point, and an of apparently smaller subunit molecular weight. Comparative pep- HPRTLondon revealed a single amino acid substitution (Ser tide mapping-experiments revealed a single abnormal tryptic pep- Leu) at position 109. -
Studies on the Mechanism of Action of 6-Mercaptopurine in Sensitive and Resistant L1210 Leukemia in Vitro*
Studies on the Mechanism of Action of 6-Mercaptopurine in Sensitive and Resistant L1210 Leukemia in Vitro* JACKD. DAVIDSON (Clinical Pharmacology and Experimental Tlierapeutics Service, National Cancer Institute, Betliesda, Md.) SUMMARY A study was made of the effects of 6-mercaptopurine (6-MP) upon nucleic acid metabolism in L1210 leukemia cells in vitro. Pharmacological concentrations of 6-MP inhibited the incorporation of both hypoxanthine and glycine into adenine nucleo- tides. Higher concentrations of 6-MP inhibited the incorporation of hypoxanthine into both adenine and guanine nucleotides. In a subline of L1210 which is resistant to 6-MP there was much less utilization of hypoxanthine than in the sensitive line, and incorporation into both adenine and guanine moieties was strongly inhibited by 6-MP. On the contrary, utilization of glycine for nucleotide purine synthesis was unaffected by 6-MP. These findings support the hypothesis that in L1210 leukemia 6-MP is metabolized to its ribotide, and this produces a metabolic block in the conversion of inosinic acid to adenylic acid. They further indicate that, in the L1210 cells resistant to 6-MP, there is a very limited capacity to convert 6-MP and hypoxanthine to ribotides. This leads to competition between 6-MP and hypoxanthine and to formation of insufficient 6-MP ribotide to cause the critical block. Although 6-mercaptopurine (6-MP) has been purines isolated from L1210 ascites leukemia cells studied with respect to its antitumor activity since have been studied. The results obtained suggest 1952, there is still relatively little information re that the primary antimetabolic activity of 6-MP garding the mechanism of its action. -
Gout: a Low-Purine Diet Makes a Difference
Patient HANDOUT Gout: A Low-Purine Diet Makes a Difference Gout occurs when high levels of uric acid in your blood cause crystals to form and build up around a joint. Your body produces uric acid when it breaks down purines. Purines occur naturally in your body, but you also get them from certain foods and drinks. By following a low-purine diet, you can help your body control the production of uric acid and lower your chances of having another gout attack. Purines are found in many healthy foods and drinks. The purpose of a low-purine diet is to lower the amount of purine that you consume each day. Avoid Beer High-Purine Foods Organ meats (e.g., liver, kidneys), bacon, veal, venison Anchovies, sardines, herring, scallops, mackerel Gravy (purines leach out of the meat during cooking so gravy made from drippings has a higher concentration of purines) Limit Moderate- Chicken, beef, pork, duck, crab, lobster, oysters, shrimp : 4-6 oz daily Purine Foods Liquor: Limit alcohol intake. There is evidence that risk of gout attack is directly related to level of alcohol consumption What Other Dietary Changes Can Help? • Choose low-fat or fat-free dairy products. Studies show that low- or non-fat milk and yogurt help reduce the chances of having a gout attack. • Drink plenty of fluids (especially water) which can help remove uric acid from your body. Avoid drinks sweetened with fructose such as soft drinks. • Eat more non-meat proteins such as legumes, nuts, seeds and eggs. • Eat more whole grains and fruits and vegetables and less refined carbohydrates, such as white bread and cakes. -
Central Nervous System Dysfunction and Erythrocyte Guanosine Triphosphate Depletion in Purine Nucleoside Phosphorylase Deficiency
Arch Dis Child: first published as 10.1136/adc.62.4.385 on 1 April 1987. Downloaded from Archives of Disease in Childhood, 1987, 62, 385-391 Central nervous system dysfunction and erythrocyte guanosine triphosphate depletion in purine nucleoside phosphorylase deficiency H A SIMMONDS, L D FAIRBANKS, G S MORRIS, G MORGAN, A R WATSON, P TIMMS, AND B SINGH Purine Laboratory, Guy's Hospital, London, Department of Immunology, Institute of Child Health, London, Department of Paediatrics, City Hospital, Nottingham, Department of Paediatrics and Chemical Pathology, National Guard King Khalid Hospital, Jeddah, Saudi Arabia SUMMARY Developmental retardation was a prominent clinical feature in six infants from three kindreds deficient in the enzyme purine nucleoside phosphorylase (PNP) and was present before development of T cell immunodeficiency. Guanosine triphosphate (GTP) depletion was noted in the erythrocytes of all surviving homozygotes and was of equivalent magnitude to that found in the Lesch-Nyhan syndrome (complete hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency). The similarity between the neurological complications in both disorders that the two major clinical consequences of complete PNP deficiency have differing indicates copyright. aetiologies: (1) neurological effects resulting from deficiency of the PNP enzyme products, which are the substrates for HGPRT, leading to functional deficiency of this enzyme. (2) immunodeficiency caused by accumulation of the PNP enzyme substrates, one of which, deoxyguanosine, is toxic to T cells. These studies show the need to consider PNP deficiency (suggested by the finding of hypouricaemia) in patients with neurological dysfunction, as well as in T cell immunodeficiency. http://adc.bmj.com/ They suggest an important role for GTP in normal central nervous system function. -
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. -
Xanthine/Hypoxanthine Assay Kit
Product Manual Xanthine/Hypoxanthine Assay Kit Catalog Number MET-5150 100 assays FOR RESEARCH USE ONLY Not for use in diagnostic procedures Introduction Xanthine and hypoxanthine are naturally occurring purine derivatives. Xanthine is created from guanine by guanine deaminase, from hypoxanthine by xanthine oxidoreductase, and from xanthosine by purine nucleoside phosphorylase. Xanthine is used as a building block for human and animal drug medications, and is an ingredient in pesticides. In vitro, xanthine and related derivatives act as competitive nonselective phosphodiesterase inhibitors, raising intracellular cAMP, activating Protein Kinase A (PKA), inhibiting tumor necrosis factor alpha (TNF-α) as well as and leukotriene synthesis. Furthermore, xanthines can reduce levels of inflammation and act as nonselective adenosine receptor antagonists. Hypoxanthine is sometimes found in nucleic acids such as in the anticodon of tRNA in the form of its nucleoside inosine. Hypoxanthine is a necessary part of certain cell, bacteria, and parasitic cultures as a substrate and source of nitrogen. For example, hypoxanthine is often a necessary component in malaria parasite cultures, since Plasmodium falciparum needs hypoxanthine to make nucleic acids as well as to support energy metabolism. Recently NASA studies with meteorites found on Earth supported the idea that hypoxanthine and related organic molecules can be formed extraterrestrially. Hypoxanthine can form as a spontaneous deamination product of adenine. Because of its similar structure to guanine, the resulting hypoxanthine base can lead to an error in DNA transcription/replication, as it base pairs with cytosine. Hypoxanthine is typically removed from DNA by base excision repair and is initiated by N- methylpurine glycosylase (MPG). -
Purine Metabolism in the Protozoan Parasite Eimeria Tenella (Hypoxanthine-Xanthine-Guanine Phosphoribosyltransferase/GMP-Agarose Affinity Column/Alopurinol) C
Proc. NatL Acad. Sci. USA Vol. 78, No. 11, pp. 6618-6622, November 1981 Biochemistry Purine metabolism in the protozoan parasite Eimeria tenella (hypoxanthine-xanthine-guanine phosphoribosyltransferase/GMP-agarose affinity column/alopurinol) C. C. WANG AND P. M. SIMASHKEVICH* Merck Institute for Therapeutic Research, Rahway, New Jersey 07065 Communicated by P. Roy Vagelos, June 25, 1981 ABSTRACT Crude extracts of the oocysts ofEimeria tenella, cidia Eimenria tenella, which develops inside the caecal epithe- a protozoan parasite of the coccidium family that develops inside lial cells ofchickens, effectively takes up hypoxanthine and pref- the caecal epithelial cells ofinfected chickens, do not incorporate erentially incorporates label from it into nucleic acids when glycine or formate into purine nucleotides; this suggests lack of grown in cell culture (13, 14). Purine metabolism in this parasite capability for de novo purine synthesis by the parasite. The ex- is particularly interesting in view of the uricotelic metabolism tracts, however, contain high levels of activity of the purine sal- of chickens and the high levels of hypoxanthine known to ac- vage enzymes: hypoxanthine, guanine, xanthine, and adenine cumulate in avian tissues phosphoribosyltransferases and adenosine kinase. The absence of (15). AMP deaminase from the parasite indicates thatE. tenella cannot In this study, we have demonstrated that E. tenella cannot convert AMP to GMP; the latter thus has to be supplied by the perform de novo purine synthesis and examined the detailed hypoxanthine, xanthine, or guanine phosphoribosyltransferase of mechanism of purine salvage. A purine phosphoribosyltrans- the parasite. These three activities are associatedwith one enzyme ferase that uses hypoxanthine and guanine as well as xanthine (HXGPRTase), which has been purified to near homogeneity in as substrates (HXGPRTase) was identified in the parasite. -
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. -
Xj 128 IUMP Glucose Substance Will Be Provisionally Referred to As UDPX (Fig
426 Studies on Uridine-Diphosphate-Glucose By A. C. PALADINI AND L. F. LELOIR Instituto de Inve8tigacione&s Bioquimicas, Fundacion Campomar, J. Alvarez 1719, Buenos Aires, Argentina (Received 18 September 1951) A previous paper (Caputto, Leloir, Cardini & found that the substance supposed to be uridine-2'- Paladini, 1950) reported the isolation of the co- phosphate was uridine-5'-phosphate. The hydrolysis enzyme of the galactose -1- phosphate --glucose - 1 - product of UDPG has now been compared with a phosphate transformation, and presented a tenta- synthetic specimen of uridine-5'-phosphate. Both tive structure for the substance. This paper deals substances were found to be identical as judged by with: (a) studies by paper chromatography of puri- chromatographic behaviour (Fig. 1) and by the rate fied preparations of uridine-diphosphate-glucose (UDPG); (b) the identification of uridine-5'-phos- 12A UDPG phate as a product of hydrolysis; (c) studies on the ~~~~~~~~~~~~~(a) alkaline degradation of UDPG, and (d) a substance similar to UDPG which will be referred to as UDPX. UMP Adenosine UDPG preparation8 8tudied by chromatography. 0 UjDPX Paper chromatography with appropriate solvents 0 has shown that some of the purest preparations of UDP UDPG which had been obtained previously contain two other compounds, uridinemonophosphate 0 4 (UMP) and a substance which appears to have the same constitution as UDPG except that it contains an unidentified component instead of glucose. This Xj 128 IUMP Glucose substance will be provisionally referred to as UDPX (Fig. la). The three components have been tested for co- enzymic activity in the galactose-1-phosphate-- 0-4 -J UDPX glucose-l-phosphate transformation, and it has been confirmed that UDPG is the active substance. -
Abiotic Synthesis of Purine and Pyrimidine Ribonucleosides in Aqueous Microdroplets
Abiotic synthesis of purine and pyrimidine ribonucleosides in aqueous microdroplets Inho Nama,b, Hong Gil Nama,c,1, and Richard N. Zareb,1 aCenter for Plant Aging Research, Institute for Basic Science, Daegu 42988, Republic of Korea; bDepartment of Chemistry, Stanford University, Stanford, CA 94305; and cDepartment of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of Korea Contributed by Richard N. Zare, November 27, 2017 (sent for review October 24, 2017; reviewed by Bengt J. F. Nordén and Veronica Vaida) Aqueous microdroplets (<1.3 μm in diameter on average) containing In a recent study, we showed a synthetic pathway for the 15 mM D-ribose, 15 mM phosphoric acid, and 5 mM of a nucleobase formation of Rib-1-P using aqueous, high–surface-area micro- (uracil, adenine, cytosine, or hypoxanthine) are electrosprayed from a droplets. This surface or near-surface reaction circumvents the capillary at +5 kV into a mass spectrometer at room temperature and fundamental thermodynamic problem of the condensation re- 2+ 1 atm pressure with 3 mM divalent magnesium ion (Mg )asacat- action (12). It has been suggested that the air–water interface alyst. Mass spectra show the formation of ribonucleosides that com- provides a favorable environment for the prebiotic synthesis of prise a four-letter alphabet of RNA with a yield of 2.5% of uridine (U), biomolecules (12–17). Using the Rib-1-P made in the above 2.5% of adenosine (A), 0.7% of cytidine (C), and 1.7% of inosine (I) during the flight time of ∼50 μs.