DOCSLIB.ORG

Is Human Hibernation Possible?

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Is Human Hibernation Possible? ANRV334-ME59-12 ARI 16 December 2007 14:50 Is Human Hibernation Possible? Cheng Chi Lee Department of Biochemistry and Molecular Biology, University of Texas Health Science Center, Houston, Texas 77030; email: [email protected] Annu. Rev. Med. 2008. 59:177–86 Key Words The Annual Review of Medicine is online at hypothermia, 5-AMP, torpor, hypometabolism http://med.annualreviews.org This article’s doi: Abstract 10.1146/annurev.med.59.061506.110403 The induction of hypometabolism in cells and organs to reduce is- Copyright c 2008 by Annual Reviews. chemia damage holds enormous clinical promise in diverse fields, in- All rights reserved cluding treatment of stroke and heart attack. However, the thought 0066-4219/08/0218-0177$20.00 that humans can undergo a severe hypometabolic state analogous to hibernation borders on science fiction. Some mammals can enter a severe hypothermic state during hibernation in which metabolic activity is extremely low, and yet full viability is restored when the animal arouses from such a state. To date, the underlying mecha- nism for hibernation or similar behaviors remains an enigma. The beneficial effect of hypothermia, which reduces cellular metabolic demands, has many well-established clinical applications. However, severe hypothermia induced by clinical drugs is extremely difficult and is associated with dramatically increased rates of cardiac arrest for nonhibernators. The recent discovery of a biomolecule, 5-AMP, which allows nonhibernating mammals to rapidly and safely enter severe hypothermia could remove this impediment and enable the wide adoption of hypothermia as a routine clinical tool. 177 ANRV334-ME59-12 ARI 16 December 2007 14:50 INTRODUCTION ing mammals. Whether chemically induced hypometabolism has any connection with the The word hibernation is often associated with natural process is not critical; observations bears taking a long winter rest. However, from these studies can be drawn upon to re- some investigators would argue that bears do veal the underlying biochemical and molecu- not really hibernate but rather enter a state lar processes of hypometabolic behaviors. of torpor. In mammals, the term torpor is of- Clinically, only mild hypothermia of 32– ten used when body temperature drops below ◦ ◦ 34 C can be induced safely by a cocktail of 31 C. Hibernation is often described as deep paralytic drugs and anesthesia (2, 3). Severe torpor. Although both words are widely used hypothermia (28◦C or lower) induced by such in the scientific literature to reflect different drug cocktails results in a high cardiac ar- degrees of a hypometabolic state, their physi- rest rate in nonhibernating mammals (4). To ological definitions are not clear. In addition, date, three classes of molecules will result some reptiles and amphibians can undergo in reversible severe hypothermia when ad- a hypometabolic process known as estivation ministered to small mammals such as mice to survive challenging environmental condi- and hamsters. Two of these are metabolic in- tions. As articulated by Heldmaier et al. (1), hibitors: 2-deoxyglucose and hydrogen sulfide “The physiological properties of daily torpor, (H2S). The third, recently identified in my hibernation and estivation are very similar. laboratory, is the end metabolite 5-adenosine The classification of hibernation, daily torpor monophosphate (5-AMP). It is the first nat- or estivation simply represents gradual differ- ural biomolecule to have this effect (5). ence in the timing, the duration and the ampli- tude of physiological inhibition.” In essence, these are hypometabolic behaviors used by an- 2-DEOXYGLUCOSE AND imals for energy conservation. On the basis HYDROGEN SULFIDE of oxygen consumption measurements, it was Hamsters are known to undergo daily tor- demonstrated that the biochemical and phys- por to conserve energy upon prolonged ex- iological events that inhibit endogenous ther- posure to low environmental temperature moregulation occur rapidly prior to the onset and short photoperiod, which mimic seasonal of hypothermia (1). In contrast, hypothermia changes (6). This torpor behavior of ham- is driven by heat loss from the body to the sters is circadian-driven. This was demon- environment. This process depends on sev- strated by experiments in which ablation eral parameters including surface/volume ra- of the suprachiamastic nucleus (SCN), the tio, the amount of fur and fat insulation, and central circadian structure, disrupts the an- the temperature gradient between the body imal’s temporal rhythm (7). After receiving and the environment. The molecular and bio- the glycolytic inhibitor 2-deoxyglucose, ham- chemical mechanisms underlying the natu- sters readily undergo torpor even when kept ral shutdown of metabolic activities remain in long photoperiod (8). In contrast, inhibi- largely unknown. tion of fatty acid metabolism by mercaptoac- The goal of this article is not to reca- etate did not induce torpor in hamsters kept pitulate the physiology of hypometabolism in long photoperiod (6). These observations that occurs naturally, as there are excellent implicate impediment of glucose utilization reviews in the literature (1). Instead, I fo- as a key event for hypometabolism. How- cus on recent attempts to mimic the induc- ever, the biochemical mechanism underlying tion of a hypometabolic state in mammals, 2-deoxyglucose induction of torpor remains which may have potential clinical applica- unclear. tions. I also offer some hypotheses on how Another metabolic inhibitor, H2S, was re- hypometabolism could occur in nonhibernat- cently found to enable mice to enter severe 178 Lee ANRV334-ME59-12 ARI 16 December 2007 14:50 hypothermia or suspended animation at a low the environment will not be adequately con- dosage of 80 ppm (9). Mice given H2S could trolled. This reasoning is consistent with the be cooled down to 15◦C into a state of sus- hypothesis that decreased ATP production or pended animation for up to six hours. Arousal utilization is involved in hibernating behav- was spontaneous, and no apparent detrimen- iors (1, 12). How these biochemical observa- tal outcome was observed after recovery. It has tions can be reconciled with the widely held been thought that a core body temperature dogma that the preoptic area of the hypotha- below 20◦C in nonhibernators will lead to car- lamus controls thermal regulatory response in diac fibrillation (10). Our lowest recording of mammals is not clear (13). core body temperature in mice during torpor induced by fasting was about 26◦C even when the ambient environmental temperature was SEARCH FOR AN ENDOGENOUS maintained at 8◦C ( J. Zhang & C.C. Lee, un- MOLECULE FOR published observations). Thus, the ability to HYPOMETABOLISM drop a nonhibernating mammal’s core body For hibernators to achieve a severe hypother- temperature to 15◦C is a major step forward. mic state, the basic principles of metabolic It suggests that nonhibernators are fully capa- biochemistry must be preserved to ensure en- ble of withstanding extreme hypometabolism. ergy homeostasis (12). This raises the possi- As with 2-deoxyglucose, the mechanism bility that such biochemical processes may be underlying H2S induction of severe hy- retained in all mammals. Mammalian organs pothermia remains unclear. H2S is a specific can be maintained in a hypothermic but highly and reversible inhibitor of cytochrome c ox- hypoxic state for many hours (14), as we see idase, a key component of the mitochondria when donor organs are transported in coolers respiratory complex IV (9). Inhibitors of the for organ transplantation. Upon transplan- mitochondria respiratory chain are toxic to tation, the restoration of blood flow and its mammals because they disrupt ATP produc- rewarming revive the basic functions of the tion by oxidative phosphorylation. Similarly, donor organ. In addition, examples from acci- 2-deoxyglucose inhibits glycolysis, which is dental hypothermia have suggested that under another biochemical process involved in the certain conditions, humans can recover fully generation of ATP and NADH from glucose from prolonged periods in severe hypother- outside of the mitochondria. Thus, the actions mia. Critically, these observations suggest that of both H2S and 2-deoxyglucose affect the nonhibernators’ organs are inherently capa- cellular production of ATP. In turn, the lower ble of withstanding extreme hypoxic stress if ATP level would downregulate biochemical their metabolic demands are reduced. Thus, reactions necessary for thermal regulation de- a project was initiated to probe the possibil- fenses. It has been observed that during hiber- ity of identifying genes from nonhibernating nation, erythrocytes and organs have signifi- mammals that are activated in an environment cantly lower ATP levels (11, 12). In particular, encountered during hibernation. the ATP level of erythrocytes from a hiber- It is widely recognized that mammals en- nating animal is ∼50% of the level observed ter hibernation in an environment of constant in a euthermic state (11). Such a large de- darkness (1). Using liver mRNA, gene expres- crease in ATP level in the erythrocyte would sion in mice exposed to regular 12:12 h cycles significantly compromise its function in regu- of light:dark (LD) was compared to gene ex- lating oxygen/carbon dioxide molecules nec- pression in mice kept in constant darkness or essary for maintaining high metabolic activity dark:dark (DD). From microarray analysis, a of the major organs. Under such conditions, it gene encoding procolipase
Load more

Recommended publications
  • The Effect of an Oral Or Intravenous Nucleotide-Free Diet on Selected Enzyme Activities in Purine Metabolism in Rats
    RICE UNIVERSITY THE EFFECT OF AN ORAL OR INTRAVENOUS NUCLEOTIDE-FREE DIET ON SELECTED ENZYME ACTIVITIES IN PURINE METABOLISM IN RATS. by SANDRA LYNN SNYDER A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE MASTER OF ARTS APPROVED, THESIS COMMITTEE: .T Dr. Frederi Associate Professor of B Chemistry Dr. Susan M. B^fget Assistant Professor of Biochemistry Dr. George J. Æchfoépfer Professor of Biochemistry and Chemistry Dr. George'N. Bennett Assistant Professor of Biochemistry Dr. Roger L. Storck Professor of Biology HOUSTON, TEXAS MARCH, 1982 ABSTRACT THE EFFECT OF AN ORAL OR INTRAVENOUS NUCLEOTIDE-FREE DIET ON SELECTED ENZYME ACTIVITIES IN PURINE METABOLISM IN RATS SANDRA LYNN SNYDER Interrelationships between purine metabolism and immunity, cancer, and the diet have been considered. In studying trends of metabolic changes which occur in response to changes in the purine content of the diet, it has been hypothesized that when purines are lacking from the diet, there is a general shift from a catabolic to an anabolic state. In the present investigation, the activities of selected enzymes on purine metabolism in rats were studied with respect to an oral or intravenous nucleotide-free diet compared to the activities in rats fed normal chow. The intravenous nucleotide-free diet caused a decrease in purine nucleoside phosphorylase activity, an increase in adenine phosphoribosyl transferase, and no change in the activity of hypoxanthine-guanine phosphoribosyl transferase, with respect to a normal control diet. The orally fed nucleotide-free diet caused a decrease in the activity of purine nucleoside phosphorylase and xanthine oxidase and increase in pancreatic ribonucléase and no change in adenine phosphoribosyl transferase or hyphoxanthine-guanine phosphoribosyl transferase, with respect to a normal control diet.
    [Show full text]
  • Enhancing Nucleotide Metabolism Protects Against Mitochondrial Dysfunction and Neurodegeneration in a PINK1 Model of Parkinson’S Disease
    ARTICLES Enhancing nucleotide metabolism protects against mitochondrial dysfunction and neurodegeneration in a PINK1 model of Parkinson's disease Roberta Tufi1, Sonia Gandhi2, Inês P. de Castro1, Susann Lehmann1, Plamena R. Angelova2, David Dinsdale1, Emma Deas2, Hélène Plun-Favreau2, Pierluigi Nicotera3, Andrey Y. Abramov2, Anne E. Willis1, Giovanna R. Mallucci1, Samantha H. Y. Loh1,4 and L. Miguel Martins1,4 Mutations in PINK1 cause early-onset Parkinson's disease (PD). Studies in Drosophila melanogaster have highlighted mitochondrial dysfunction on loss of Pink1 as a central mechanism of PD pathogenesis. Here we show that global analysis of transcriptional changes in Drosophila pink1 mutants reveals an upregulation of genes involved in nucleotide metabolism, critical for neuronal mitochondrial DNA synthesis. These key transcriptional changes were also detected in brains of PD patients harbouring PINK1 mutations. We demonstrate that genetic enhancement of the nucleotide salvage pathway in neurons of pink1 mutant flies rescues mitochondrial impairment. In addition, pharmacological approaches enhancing nucleotide pools reduce mitochondrial dysfunction caused by Pink1 deficiency. We conclude that loss of Pink1 evokes the activation of a previously unidentified metabolic reprogramming pathway to increase nucleotide pools and promote mitochondrial biogenesis. We propose that targeting strategies enhancing nucleotide synthesis pathways may reverse mitochondrial dysfunction and rescue neurodegeneration in PD and, potentially, other diseases linked to mitochondrial impairment. The role of mitochondrial impairment in PD has long been debated. By combining transcriptional and metabolic profiling, we have Recently, the identification of causative mutations in PINK1, a gene uncovered significant alterations in the nucleotide metabolism encoding a mitochondrial kinase in PD patients has renewed interest in networks of pink1 mutant flies.
    [Show full text]
  • Navigating Metabolism
    This is a free sample of content from Navigating Metabolism. Click here for more information on how to buy the book. Index Page references followed by b denote boxes; those followed by f denote figures; those followed by t denote tables. A Acyl-CoA synthetase, 110 Acyl transacylase, 107, 109f ACC (acetyl-CoA carboxylase), 105, 107, Adenine, 148, 149f, 155, 157f. 109f, 113, 115, 117, 173 See also Purines Acetate, 182, 193 Adenine nucleotide transporter (ANT), 38, Acetoacetate, 116b, 117b 47f, 53, 56–57 Acetone, 116b, 117b Adenosine, 142, 143f, 164–165, 164f Acetylation, 181–183, 184f Adenosine deaminase, 165 acetyl-CoA and, 9, 10f, 181–183, 184f Adenosine phosphoribosyltransferase (APRT), of lysine residues, 2, 183 155, 157f Acetyl-CoA, 2 Adenylate kinase, 16, 32, 112, 152, 154f allosteric regulation of pyruvate Adenylosuccinate, 152, 154f–155f carboxylase, 93 ADP from citrate, 43, 53, 56f, 59, 60f, 71, 72f, adenine nucleotide transporter (ANT), 38, 47f, 107, 108f 53, 56–57 citrate transporter and, 53–54, 56f adenylate kinase reaction, 16, 32, 112 entry into TCA cycle, 41, 42f energy charge, 18 in fatty acid synthesis, 107–110, 108f–109f P2 purinoreceptor activation, generation of, 39, 41, 42f, 43, 45, 45f, 164, 164f 53–54, 56f, 59 Aerobic glycolysis, 34–35, 190, 220 metabolic functions, 9, 10f, 53 Aging posttranslational modifications and, free radical theory of, 83b 181–183, 184f metabolism and, 212 Acetyl-CoA carboxylase (ACC), 105, 107, AKT, 120, 168f, 169–170, 199 109f, 113, 115, 117, 173 Alanine Acetylserotonin O-methyltransferase, β-alanine, 161–162, 163f 139, 140f conversion to pyruvate, 93 Aconitase, 60, 70 generation of, 130, 132f Activation energy, 13, 13f, 18 from pyruvate, 26 Active site, 20 urea cycle and, 134 Acyclglycerophosphate acyltransferase, 110, 111f Alanine aminotransferase, 134 ACYL (ATP-citrate lyase), 53, 56f, 59, 71, Albinism, 41 72f, 107, 108f, 182, 192 Alcohol dehydrogenase, 31f 233 © 2015 by Cold Spring Harbor Laboratory Press.
    [Show full text]
  • Journal Vol 18 No 1 & 2, September 2002
    Journal of the British Dragonfly Society Volume 18 Number I & 2 September 2002 Editor Dr Jonathan Pickup TheJournal ofthe Bn/ish DragonflySociely, published twice a year, contains articleson Odonata that have been recorded from the United Kingdom and articles on EuropeanOdonata written by members of the Society. The aims of the British Dragonfly Society(B.D.S.) are to promote and encourage the study and conservation ofOdonata and their natural habitats, especially in the United Kingdom. Trustees of the British Dragonfly Society Articles for publicanon (twopaper copes er ('.Ir copy plus disk please) should be sent rothe Chairman: T G. Beynon Editor. Instructions for authors appor inside Vice�Chairma,,: PM. AUen back cover. SecrellJry: W. H. Wain '1rriJJuru: A. G. T Carter Back numbers of the Journal can be purchased Edilnr, J. Pickup from the Librarian/Archivist at ConV<nOrof Dragonfly ConstnJal"'" Group, 1-4 copies £2.75 percopy, P Taylor 5 copies or over £2.60 per copy (members) or £5.50 (non-mcmbe.. ). Ordinary Trustees: M. T Avcrill Ordinary membership annual subscription D.J. Pryce D. Gennard £10.00. D. J. Mann Overseas subscription £12.50. All subscriptions are due on 1st April each year. Late payers will be charged £1 extra. ADDRESSES Life membership subscription £1000. Edilor: Jonathan Pickup, Other subscription rates (library, corporate) on 129 Craigleith Road, application to the Secretary, who will also deal Edinburgh EH4 2EH with membership enquiries. e�mail: [email protected] SW'eUJry: W. H. Wain, The Haywain, Hollywater Road, Bordon, Hants GU35 OAD Ubrarian/Arr:III'VtSl: D.
    [Show full text]
  • 1 Targeting Subtype-Specific Metabolic Preferences in Nucleotide
    bioRxiv preprint doi: https://doi.org/10.1101/2020.04.19.049577; this version posted May 9, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. Targeting subtype-specific metabolic preferences in nucleotide biosynthesis inhibits tumor growth in a breast cancer model Martin P. Ogrodzinski1,2, Shao Thing Teoh1, and Sophia Y. Lunt1,3* 1Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA 2Department of Physiology, Michigan State University, East Lansing, MI, USA 3Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, MI, USA *Correspondence: Sophia Y. Lunt, Ph.D. Biochemistry Building 603 Wilson Rd Room 522A Michigan State University East Lansing, MI 48824, USA Phone: 517-432-4886 Email: [email protected] 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.04.19.049577; this version posted May 9, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. ABSTRACT Investigating metabolic rewiring in cancer can lead to the discovery of new treatment strategies for breast cancer subtypes that currently lack targeted therapies. Using MMTV- Myc driven tumors to model breast cancer heterogeneity, we investigated metabolic differences between two histological subtypes, the epithelial-mesenchymal transition (EMT) and the papillary subtypes, using a combination of genomic and metabolomic techniques. We identified differences in nucleotide metabolism between EMT and papillary subtypes: EMT tumors preferentially use the nucleotide salvage pathway, while papillary tumors prefer de novo nucleotide biosynthesis.
    [Show full text]
  • When the Reaction Is
    Table S3. iJL1678-ME model modification (blocked reactions) Iter. Cat. ID Name Formula Subsystem Comments (When the reaction is turned on) 1 bp2 EDD 6-phosphogluconate dehydratase 6pgc_c⇌2ddg6p_c + h2o_c Pentose Phosphate Pathway Create a major effect of steep acetate overflow elevation in high growth. Comparing to the main glycolytic pathway, it is metabolicly less efficient but proteomicly more efficient. bp1 ICL Isocitrate lyase icit_c→glx_c + succ_c Anaplerotic Reactions Bypass for the main TCA cycle pathways from turning isocitrate to succinate, when ICL is turned on, Isocitrate dehydrogenase(ICDHyr), 2-Oxogluterate dehydrogenase(AKGDH) and Succinyl-CoA synthetase (ATP-forming,SUCOAS) would reduce. Ref. (1) and (2) shows that this reaction is off in higher growth. Ref. (3) shows that this reaction is converging to being off when the dynamic of respiration using enzyme kinetics is simulated. 2 bp1 ABTA 4-aminobutyrate transaminase 4abut_c + akg_c⇌glu__L_c + sucsal_c Arginine and Proline Metabolism Another backup pathway of succinate production, from 2-Oxoglutarate (akg). Respiration would be induced when it is on, since the flux through ETC(CYTBO3_4pp and ATPS4rpp) would increase. As it requires the co-factor pyridoxal 5'-phosphate(2−) to get catalyzed(4), indicating that this reaction is regulated by the flux of other reactions(pyridoxal 5'- phosphate(2-) production, etc.). 3 GLYAT Glycine C-acetyltransferase accoa_c + gly_c⇌2aobut_c + coa_c Glycine and Serine Metabolism A reaction that back up for the respiration. Reactions fluxes in TCA cycle would drop when this reaction is turned on. It also requires pyridoxal 5'-phosphate(2−) for the regulation. 4 NADTRHD NAD transhydrogenase nad_c + nadph_c⇌nadh_c + nadp_c Oxidative Phosphorylation A reaction that would make the transition between NAD and NADP metabolically more efficient.
    [Show full text]
  • Emerging Roles of Nucleotide Metabolism in Cancer Development: Progress and Prospect
    www.aging-us.com AGING 2021, Vol. 13, No. 9 Review Emerging roles of nucleotide metabolism in cancer development: progress and prospect Jingsong Ma1,2, Mengya Zhong1,2, Yubo Xiong1,2, Zhi Gao3, Zhengxin Wu4, Yu Liu5, Xuehui Hong1,2 1Institute of Gastrointestinal Oncology, School of Medicine, Xiamen University, Fujian, Xiamen 361000, China 2Department of Gastrointestinal Surgery, Zhongshan Hospital, Xiamen University, Fujian, Xiamen 361000, China 3National Center for International Research of Biological Targeting Diagnosis and Therapy, Guangxi Key Laboratory of Biological Targeting Diagnosis and Therapy Research, Guangxi Medical University, Guangxi, Nanning 53000, China 4Medical College of Guangxi University, Guangxi, Nanning 530000, China 5General Surgery Center, Bazhong Central Hospital, Sichuan, Bazhong 636000, China Correspondence to: Xuehui Hong; email: [email protected] Keywords: nucleotide metabolism, tumor immunity, key metabolic enzyme, signaling pathway, oncogene-induced senescence Received: August 12, 2020 Accepted: March 29, 2021 Published: May 5, 2021 Copyright: © 2021 Ma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Abnormal cancer metabolism occurs throughout the development of tumors. Recent studies have shown that abnormal nucleotide metabolism not only accelerates the development of tumors but also inhibits the normal immune response in the tumor microenvironment. Although few relevant experiments and reports are available, study of the interaction between nucleotide metabolism and cancer development is rapidly developing. The intervention, alteration or regulation of molecular mechanisms related to abnormal nucleotide metabolism in tumor cells has become a new idea and strategy for the treatment of tumors and prevention of recurrence and metastasis.
    [Show full text]
  • Reports Report
    Cell Reports Report Rhythmic Nucleotide Synthesis in the Liver: Temporal Segregation of Metabolites Jean-Michel Fustin,1 Masao Doi,1 Hiroyuki Yamada,1 Rie Komatsu,1 Shigeki Shimba,2 and Hitoshi Okamura1,* 1Department of System Biology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimo-Adachi-cho, Sakyo-ku, Kyoto 606-8501, Japan 2Department of Health Science, College of Pharmacy, Nihon University, Funabashi, Chiba 274-8555, Japan *Correspondence: [email protected] DOI 10.1016/j.celrep.2012.03.001 SUMMARY (Bmal1LÀ/À), which show rhythmic activity and food intake but lack a functional molecular clock in the liver driving hepatic phys- The synthesis of nucleotides in the body is centrally iology (Shimba et al., 2011). We show that the expression of rate- controlled by the liver, via salvage or de novo limiting enzymes in nucleotide metabolism is under clock control, synthesis. We reveal a pervasive circadian influence and that nucleotides are rhythmic and time segregated. In LÀ/À on hepatic nucleotide metabolism, from rhythmic Bmal1 liver, aberrant expression of these enzymes is corre- gene expression of rate-limiting enzymes to oscil- lated with the disruption of nucleotide rhythms. In particular, lating nucleotide metabolome in wild-type (WT) ATP and was constantly low and uric acid was increased, sug- gesting inefficient purine synthesis and/or increased degrada- mice. Genetic disruption of the hepatic clock leads tion. We here provide the first (to our knowledge) integrated tran- to aberrant expression of these enzymes, together scriptome and metabolome circadian timetable focused on with anomalous nucleotide rhythms, such as a single metabolic pathway, giving insights into the physiological constant low levels of ATP with an excess in uric importance of the local hepatic clock for nucleotide synthesis.
    [Show full text]
  • Nucleotide Metabolism Pathway: the Achilles' Heel for Bacterial Pathogens
    REVIEW ARTICLES Nucleotide metabolism pathway: the achilles’ heel for bacterial pathogens Sujata Kumari1,2,* and Prajna Tripathi1,3 1National Institute of Immunology, New Delhi 110 067, India 2Present address: Department of Zoology, Magadh Mahila College, Patna University, Patna 800 001, India 3Present address: Institute of Molecular Medicine, Jamia Hamdard, New Delhi 110 062, India de novo pathway, the nucleotides are synthesized from Pathogens exploit their host to extract nutrients for their survival. They occupy a diverse range of host simple precursor molecules. In the salvage pathway, the niches during infection which offer variable nutrients preformed nucleobases or nucleosides which are present accessibility. To cause a successful infection a patho- in the cell or transported from external environmental gen must be able to acquire these nutrients from the milieu to the cell are utilized to form nucleotides. host as well as be able to synthesize the nutrients on its own, if required. Nucleotides are the essential me- tabolite for a pathogen and also affect the pathophysi- Purine biosynthesis pathway ology of infection. This article focuses on the role of nucleotide metabolism of pathogens during infection The purine biosynthesis pathway is universally conserved in a host. Nucleotide metabolism and disease pathoge- in living organisms (Figure 1). As an example, we here nesis are closely related in various pathogens. Nucleo- present the pathway derived from well-studied Gram- tides, purines and pyrimidines, are biosynthesized by positive bacteria Lactococcus lactis. In the de novo the de novo and salvage pathways. Whether the patho- pathway the purine nucleotides are synthesized from sim- gen will employ the de novo or salvage pathway dur- ple molecules such as phosphoribosyl pyrophosphate ing infection is dependent on various factors, like (PRPP), amino acids, CO2 and NH3 by a series of enzy- availability of nucleotides, energy condition and pres- matic reactions.
    [Show full text]
  • Starting the Winter Season: Predicting Endodormancy Induction Through Multi-Process Modeling. Guillaume Charrier
    Starting the winter season: predicting endodormancy induction through multi-process modeling. Guillaume Charrier To cite this version: Guillaume Charrier. Starting the winter season: predicting endodormancy induction through multi- process modeling.. 2021. hal-03065757v2 HAL Id: hal-03065757 https://hal.inrae.fr/hal-03065757v2 Preprint submitted on 31 Mar 2021 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. 1 Starting the winter season: predicting endodormancy induction in walnut 2 trees through multi-process modeling. 3 4 Running title: Predicting endodormancy induction in walnut trees 5 6 Guillaume Charrier1 7 1Université Clermont Auvergne, INRAE, PIAF, 63000 Clermont-Ferrand, France 8 *: corresponding author 9 Email: [email protected] 10 Tel: +33 4 43 76 14 21 11 UMR PIAF, INRAE Site de Crouel 12 5, chemin de Beaulieu 13 63000 Clermont-Ferrand 14 1 1 Abstract 2 Background and Aims 3 In perennial plants, the annual phenological cycle is sub-divided into successive stages whose 4 completion will lead directly to the onset of the following event. A critical point is the transition 5 between the apparent vegetative growth and the cryptic dormancy. To date, the initial date for 6 chilling accumulation (DCA) is arbitrarily set using various rules such as fixed or dynamic dates 7 depending on environmental variables.
    [Show full text]
  • What's That Big Building Going up in Carter?
    Volume 3, Issue 1 Land & Natural Resources Quarterly Newsletter J a n u a r y — March 2013 Potawatomi Forest County What’s That Big Building Going Up In Carter? The dance arbor floor is constructed from I n s i d e he Forest County Potawatomi 100% recycled rubber scrap tires that would this issue: T Powwow Grounds!! otherwise be land filled. P l a n n i n g 1 The Forest County Potawatomi Community Department is constructing a permanent Powwow Grounds just down the hill from the W a t e r 2 - Potawatomi Carter Casino in Carter, WI. Department 3 The project includes a Dance Arbor, Show- N e w 4 er, Restrooms, Parking Area, Camping, Fire Pit and Kitchen/Social Arbor. E m p l o y e e s W i l d l i f e 5 - Every year millions of rubber tires are thrown away and are one of the most prob- 6 Earth Friendly. Each 24" x 24" lematic sources of waste. Safety tile is made from scrap tires. B o t a n y / 7 - W e t l a n d s 8 P h o t o s 9 C o n t a c t s 9 If you have any questions regarding the Powwow Grounds or would like a tour please contact the FCPC Planning Department at 715/478-4944. Land & Natural Resources Quarterly Newsletter Page 2 Bug Lake Winter Fisheree Adult Youth Northern Pike Northern Pike FCPC Natural Joe Shepard 34 3/4” Israel Alloway 22 1/4” Resources Jamie Tuckwab 18” Ryana Alloway 17” Jason Spaude 15 1/4” Hunter Tuckwab 16 1/2” Department once again hosted the Largemouth Bass Largemouth Bass annual Bug Lake Joe Brown Sr.
    [Show full text]
  • ATP Precursor Depletion and Postischemic Myocardial Recovery'
    JOURNAL OF SURGICAL RESEARCH 50,629-633 (19%) ATP Precursor Depletion and Postischemic Myocardial Recovery’ STEVENF. BOLLING, M.D.,2 EDWARDL. BOVE, M.D., AND KIM P. GALLAGHER,PH.D. Thoracic Surgery Research Laboratory, Departments of Surgery (Section of Thoracic Surgery) and Physiology, Uniuersity of Michigan Medical School, Ann Arbor, Michigan 48109 Presented at the Annual Meeting of the Association for Academic Surgery, Houston, Texas, November 14-17, 1990 lized routinely. Despite these protective techniques, how- Although cardioplegia reduces myocardial metabo- ever, adenosine triphosphate (ATP) depletion may oc- lism during ischemia, adenosine triphosphate (ATP) cur during ischemia. The slow recovery of the depleted depletion occurs, which may contribute to poor func- nucleotides, especially ATP, following ischemia is well tional recovery after reperfusion. Augmenting myo- recognized. Since intracellular ATP is essential for myo- cardial adenosine during ischemia is successful in im- cardial contraction and relaxation, ATP depletion may proving ATP repletion and myocardial recovery follow- be an important factor contributing to the incomplete ing ischemia. If adenosine is an important determinant recovery of ventricular function following ischemia and of ischemic tolerance, then depletion or elimination of reperfusion. The decrease in ATP during ischemia is not myocardial adenosine should lead to poor functional accompanied by a rise in ADP, as ADP is quickly trans- and metabolic recovery after ischemia. To test this hy- formed to AMP. The dephosphorylation of AMP by pothesis, isolated, perfused rabbit hearts were sub- 5’-nucleotidase results in formulation of adenosine jected to 120 min of 34°C ischemia. Hearts received St. which is deaminated to inosine by adenosine deaminase.
    [Show full text]