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[PMID]:28380374
[Au] Autor:Bertholet AM; Kazak L; Chouchani ET; Bogaczynska MG; Paranjpe I; Wainwright GL; Bétourné A; Kajimura S; Spiegelman BM; Kirichok Y
[Ad] Endereço:Department of Physiology, University of California, San Francisco, San Francisco, CA 94143, USA.
[Ti] Título:Mitochondrial Patch Clamp of Beige Adipocytes Reveals UCP1-Positive and UCP1-Negative Cells Both Exhibiting Futile Creatine Cycling.
[So] Source:Cell Metab;25(4):811-822.e4, 2017 Apr 04.
[Is] ISSN:1932-7420
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cold and other environmental factors induce "browning" of white fat depots-development of beige adipocytes with morphological and functional resemblance to brown fat. Similar to brown fat, beige adipocytes are assumed to express mitochondrial uncoupling protein 1 (UCP1) and are thermogenic due to the UCP1-mediated H leak across the inner mitochondrial membrane. However, this assumption has never been tested directly. Herein we patch clamped the inner mitochondrial membrane of beige and brown fat to provide a direct comparison of their thermogenic H leak (I ). All inguinal beige adipocytes had robust UCP1-dependent I comparable to brown fat, but it was about three times less sensitive to purine nucleotide inhibition. Strikingly, only âˆ¼15% of epididymal beige adipocytes had I , while in the rest UCP1-dependent I was undetectable. Despite the absence of UCP1 in the majority of epididymal beige adipocytes, these cells employ prominent creatine cycling as a UCP1-independent thermogenic mechanism.
[Mh] Termos MeSH primário: Adipócitos Bege/metabolismo
Creatina/metabolismo
Mitocôndrias/metabolismo
Técnicas de Patch-Clamp
Proteína Desacopladora 1/metabolismo
[Mh] Termos MeSH secundário: Adipócitos Bege/efeitos dos fármacos
Tecido Adiposo Marrom/metabolismo
Animais
Respiração Celular/efeitos dos fármacos
Epididimo/metabolismo
Ácidos Graxos/metabolismo
Canal Inguinal/fisiologia
Masculino
Camundongos
Mitocôndrias/efeitos dos fármacos
Fosforilação Oxidativa/efeitos dos fármacos
Prótons
Nucleotídeos de Purina/farmacologia
Receptores Adrenérgicos beta 3/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fatty Acids); 0 (Protons); 0 (Purine Nucleotides); 0 (Receptors, Adrenergic, beta-3); 0 (Uncoupling Protein 1); MU72812GK0 (Creatine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171029
[Lr] Data última revisão:
171029
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170406
[St] Status:MEDLINE


  2 / 1686 MEDLINE  
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[PMID]:28111214
[Au] Autor:Ma EH; Bantug G; Griss T; Condotta S; Johnson RM; Samborska B; Mainolfi N; Suri V; Guak H; Balmer ML; Verway MJ; Raissi TC; Tsui H; Boukhaled G; Henriques da Costa S; Frezza C; Krawczyk CM; Friedman A; Manfredi M; Richer MJ; Hess C; Jones RG
[Ad] Endereço:Goodman Cancer Research Centre, McGill University, Montreal, QC H3A 1A3, Canada; Department of Physiology, McGill University, Montreal, QC H3G 1Y6, Canada.
[Ti] Título:Serine Is an Essential Metabolite for Effector T Cell Expansion.
[So] Source:Cell Metab;25(2):345-357, 2017 Feb 07.
[Is] ISSN:1932-7420
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:During immune challenge, T lymphocytes engage pathways of anabolic metabolism to support clonal expansion and the development of effector functions. Here we report a critical role for the non-essential amino acid serine in effector T cell responses. Upon activation, T cells upregulate enzymes of the serine, glycine, one-carbon (SGOC) metabolic network, and rapidly increase processing of serine into one-carbon metabolism. We show that extracellular serine is required for optimal T cell expansion even in glucose concentrations sufficient to support T cell activation, bioenergetics, and effector function. Restricting dietary serine impairs pathogen-driven expansion of T cells in vivo, without affecting overall immune cell homeostasis. Mechanistically, serine supplies glycine and one-carbon units for de novo nucleotide biosynthesis in proliferating T cells, and one-carbon units from formate can rescue T cells from serine deprivation. Our data implicate serine as a key immunometabolite that directly modulates adaptive immunity by controlling T cell proliferative capacity.
[Mh] Termos MeSH primário: Metaboloma
Serina/metabolismo
Linfócitos T/citologia
Linfócitos T/metabolismo
[Mh] Termos MeSH secundário: Animais
Carbono/metabolismo
Pontos de Checagem do Ciclo Celular
Proliferação Celular
Dieta
Metabolismo Energético
Espaço Extracelular/metabolismo
Glicina
Listeria monocytogenes/imunologia
Redes e Vias Metabólicas
Camundongos Endogâmicos C57BL
Nucleotídeos de Purina/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Purine Nucleotides); 452VLY9402 (Serine); 7440-44-0 (Carbon); TE7660XO1C (Glycine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170124
[St] Status:MEDLINE


  3 / 1686 MEDLINE  
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[PMID]:28057583
[Au] Autor:Crichton PG; Lee Y; Kunji ER
[Ad] Endereço:Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich NR4 7TJ, United Kingdom. Electronic address: P.Crichton@uea.ac.uk.
[Ti] Título:The molecular features of uncoupling protein 1 support a conventional mitochondrial carrier-like mechanism.
[So] Source:Biochimie;134:35-50, 2017 Mar.
[Is] ISSN:1638-6183
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Uncoupling protein 1 (UCP1) is an integral membrane protein found in the mitochondrial inner membrane of brown adipose tissue, and facilitates the process of non-shivering thermogenesis in mammals. Its activation by fatty acids, which overcomes its inhibition by purine nucleotides, leads to an increase in the proton conductance of the inner mitochondrial membrane, short-circuiting the mitochondrion to produce heat rather than ATP. Despite 40 years of intense research, the underlying molecular mechanism of UCP1 is still under debate. The protein belongs to the mitochondrial carrier family of transporters, which have recently been shown to utilise a domain-based alternating-access mechanism, cycling between a cytoplasmic and matrix state to transport metabolites across the inner membrane. Here, we review the protein properties of UCP1 and compare them to those of mitochondrial carriers. UCP1 has the same structural fold as other mitochondrial carriers and, in contrast to past claims, is a monomer, binding one purine nucleotide and three cardiolipin molecules tightly. The protein has a single substrate binding site, which is similar to those of the dicarboxylate and oxoglutarate carriers, but also contains a proton binding site and several hydrophobic residues. As found in other mitochondrial carriers, UCP1 has two conserved salt bridge networks on either side of the central cavity, which regulate access to the substrate binding site in an alternating way. The conserved domain structures and mobile inter-domain interfaces are consistent with an alternating access mechanism too. In conclusion, UCP1 has retained all of the key features of mitochondrial carriers, indicating that it operates by a conventional carrier-like mechanism.
[Mh] Termos MeSH primário: Cardiolipinas/metabolismo
Ácidos Graxos/metabolismo
Mitocôndrias/metabolismo
Prótons
Termogênese/fisiologia
Proteína Desacopladora 1/química
[Mh] Termos MeSH secundário: Adipócitos Marrons/citologia
Adipócitos Marrons/metabolismo
Tecido Adiposo Marrom/citologia
Tecido Adiposo Marrom/metabolismo
Animais
Metabolismo Energético/fisiologia
Regulação da Expressão Gênica
Seres Humanos
Transporte de Íons
Mitocôndrias/genética
Modelos Moleculares
Nucleotídeos de Purina/metabolismo
Proteína Desacopladora 1/genética
Proteína Desacopladora 1/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Cardiolipins); 0 (Fatty Acids); 0 (Protons); 0 (Purine Nucleotides); 0 (Uncoupling Protein 1)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170107
[St] Status:MEDLINE


  4 / 1686 MEDLINE  
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[PMID]:27989503
[Au] Autor:Ferrari D; Malavasi F; Antonioli L
[Ad] Endereço:Department of Life Science and Biotechnology, University of Ferrara, Ferrara, Italy. Electronic address: davide.ferrari@unife.it.
[Ti] Título:A Purinergic Trail for Metastases.
[So] Source:Trends Pharmacol Sci;38(3):277-290, 2017 Mar.
[Is] ISSN:1873-3735
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Nucleotides and nucleosides have emerged as important modulators of tumor biology. Recently acquired evidence shows that, when these molecules are released by cancer cells or surrounding tissues, they act as potent prometastatic factors, favoring tumor cell migration and tissue colonization. Therefore, nucleotides and nucleosides should be considered as a new class of prometastatic factors. In this review, we focus on the prometastatic roles of nucleotides and discuss future applications of purinergic signaling modulation in view of antimetastatic therapies.
[Mh] Termos MeSH primário: Neoplasias/metabolismo
Neoplasias/patologia
Nucleosídeos de Purina/metabolismo
Nucleotídeos de Purina/metabolismo
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Metástase Neoplásica
Receptores Purinérgicos P1/metabolismo
Receptores Purinérgicos P2/metabolismo
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Purine Nucleosides); 0 (Purine Nucleotides); 0 (Receptors, Purinergic P1); 0 (Receptors, Purinergic P2)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161220
[St] Status:MEDLINE


  5 / 1686 MEDLINE  
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[PMID]:27838211
[Au] Autor:Zhang JD; Zhang FX; Guo LF; Li N; Shan BE
[Ad] Endereço:Research Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, PR China; Clinical Laboratory, Harrison International Peace Hospital of Hebei Medical University, Hengshui, Hebei 050000, PR China.
[Ti] Título:Chronic alcohol administration affects purine nucleotide catabolism in vivo.
[So] Source:Life Sci;168:58-64, 2017 Jan 01.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIMS: To investigate the relationship between chronic alcohol administration and purine nucleotide metabolism in vivo. MAIN METHODS: Rat models of alcohol dependence and withdrawal were used. The concentrations of uric acid (UAC), urea nitrogen (UREA), creatinine (CREA), and beta-2-microglobulin (ß2-M) and creatinine clearance rate (CCR) in plasma were measured. The PLC method was used to detect the absolute content of purine nucleotides in different tissues. Enzymatic activities of adenosine deaminase (ADA), xanthine oxidase (XO), ribose 5-phosphate pyrophosphokinase (RPPPK), glutamine phosphoribosylpyrophosphate amidotransferase (GPRPPAT), hypoxanthine-guanine phosphate ribose transferase (HGPRT), and adenine phosphoribosyltransferase (APRT) in the tissues were analyzed. Real-time PCR was used to determine the relative level of ADA and XO. KEY FINDINGS: The renal function of rats with alcohol dependence was normal. Further, the content of purine nucleotides (GMP, AMP, GTP, and ATP) in tissues of the rats was decreased, which indicated that the increased uric acid should be derived from the decomposition of nucleotides in vivo. The activity of XO and ADA increased, and their mRNA expression was enhanced in the alcohol dependence group, but there was no significant difference in the activity of RPPPK and GPRPPAT in the liver, small intestine, and muscle; furthermore, no significant difference in the activity of HGPRT and APRT was observed in the brain. SIGNIFICANCE: These results indicate that chronic alcohol administration might enhance the catabolism of purine nucleotides in tissues by inducing gene expression of ADA and XO, leading to elevation of plasma uric acid levels.
[Mh] Termos MeSH primário: Alcoolismo/metabolismo
Nucleotídeos de Purina/metabolismo
[Mh] Termos MeSH secundário: Alcoolismo/sangue
Alcoolismo/genética
Alcoolismo/fisiopatologia
Animais
Regulação da Expressão Gênica
Rim/metabolismo
Rim/fisiopatologia
Nucleotídeos de Purina/genética
Ratos
Ratos Sprague-Dawley
Ácido Úrico/sangue
Ácido Úrico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Purine Nucleotides); 268B43MJ25 (Uric Acid)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170201
[Lr] Data última revisão:
170201
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161114
[St] Status:MEDLINE


  6 / 1686 MEDLINE  
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[PMID]:27780585
[Au] Autor:Menzies RI; Tam FW; Unwin RJ; Bailey MA
[Ad] Endereço:British Heart Foundation Centre for Cardiovascular Science, The University of Edinburgh, Edinburgh, Scotland, UK.
[Ti] Título:Purinergic signaling in kidney disease.
[So] Source:Kidney Int;91(2):315-323, 2017 Feb.
[Is] ISSN:1523-1755
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Nucleotides are key subunits for nucleic acids and provide energy for intracellular metabolism. They can also be released from cells to act physiologically as extracellular messengers or pathologically as danger signals. Extracellular nucleotides stimulate membrane receptors in the P2 and P1 family. P2X are ATP-activated cation channels; P2Y and P1 are G-protein coupled receptors activated by ATP, ADP, UTP, and UDP in the case of P2 or adenosine for P1. Renal P2 receptors influence both vascular contractility and tubular function. Renal cells also express ectonucleotidases that rapidly hydrolyze extracellular nucleotides. These enzymes integrate this multireceptor purinergic-signaling complex by determining the nucleotide milieu to titrate receptor activation. Purinergic signaling also regulates immune cell function by modulating the synthesis and release of various cytokines such as IL1-ß and IL-18 as part of inflammasome activation. Abnormal or excessive stimulation of this intricate paracrine system can be pro- or anti-inflammatory, and is also linked to necrosis and apoptosis. Kidney tissue injury causes a localized increase in ATP concentration, and sustained activation of P2 receptors can lead to renal glomerular, tubular, and vascular cell damage. Purinergic receptors also regulate the activity and proliferation of fibroblasts, promoting both inflammation and fibrosis in chronic disease. In this short review we summarize some of the recent findings related to purinergic signaling in the kidney. We focus predominantly on the P2X7 receptor, discussing why antagonists have so far disappointed in clinical trials and how advances in our understanding of purinergic signaling might help to reposition these compounds as potential treatments for renal disease.
[Mh] Termos MeSH primário: Adenosina/metabolismo
Nefropatias/metabolismo
Rim/metabolismo
Nucleotídeos de Purina/metabolismo
Receptores Purinérgicos P1/metabolismo
Receptores Purinérgicos P2/metabolismo
Transdução de Sinais
[Mh] Termos MeSH secundário: Animais
Seres Humanos
Rim/efeitos dos fármacos
Rim/patologia
Rim/fisiopatologia
Nefropatias/tratamento farmacológico
Nefropatias/patologia
Nefropatias/fisiopatologia
Ligantes
Antagonistas do Receptor Purinérgico P2X/uso terapêutico
Receptores Purinérgicos P1/efeitos dos fármacos
Receptores Purinérgicos P2/efeitos dos fármacos
Receptores Purinérgicos P2X7/efeitos dos fármacos
Receptores Purinérgicos P2X7/metabolismo
Transdução de Sinais/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Ligands); 0 (P2XR receptor, human); 0 (Purine Nucleotides); 0 (Purinergic P2X Receptor Antagonists); 0 (Receptors, Purinergic P1); 0 (Receptors, Purinergic P2); 0 (Receptors, Purinergic P2X7); K72T3FS567 (Adenosine)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171101
[Lr] Data última revisão:
171101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161027
[St] Status:MEDLINE


  7 / 1686 MEDLINE  
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[PMID]:27751905
[Au] Autor:Woyda-Ploszczyca AM; Jarmuszkiewicz W
[Ad] Endereço:Laboratory of Bioenergetics, Faculty of Biology, Adam Mickiewicz University, Umultowska 89, 61-614 Poznan, Poland.
[Ti] Título:The conserved regulation of mitochondrial uncoupling proteins: From unicellular eukaryotes to mammals.
[So] Source:Biochim Biophys Acta;1858(1):21-33, 2017 01.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Uncoupling proteins (UCPs) belong to the mitochondrial anion carrier protein family and mediate regulated proton leak across the inner mitochondrial membrane. Free fatty acids, aldehydes such as hydroxynonenal, and retinoids activate UCPs. However, there are some controversies about the effective action of retinoids and aldehydes alone; thus, only free fatty acids are commonly accepted positive effectors of UCPs. Purine nucleotides such as GTP inhibit UCP-mediated mitochondrial proton leak. In turn, membranous coenzyme Q may play a role as a redox state-dependent metabolic sensor that modulates the complete activation/inhibition of UCPs. Such regulation has been observed for UCPs in microorganisms, plant and animal UCP1 homologues, and UCP1 in mammalian brown adipose tissue. The origin of UCPs is still under debate, but UCP homologues have been identified in all systematic groups of eukaryotes. Despite the differing levels of amino acid/DNA sequence similarities, functional studies in unicellular and multicellular organisms, from amoebae to mammals, suggest that the mechanistic regulation of UCP activity is evolutionarily well conserved. This review focuses on the regulatory feedback loops of UCPs involving free fatty acids, aldehydes, retinoids, purine nucleotides, and coenzyme Q (particularly its reduction level), which may derive from the early stages of evolution as UCP first emerged.
[Mh] Termos MeSH primário: Aldeídos/metabolismo
Eucariotos/metabolismo
Ácidos Graxos não Esterificados/metabolismo
Mamíferos/metabolismo
Proteínas de Desacoplamento Mitocondrial/metabolismo
Nucleotídeos de Purina/metabolismo
Ubiquinona/metabolismo
[Mh] Termos MeSH secundário: Animais
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Aldehydes); 0 (Fatty Acids, Nonesterified); 0 (Mitochondrial Uncoupling Proteins); 0 (Purine Nucleotides); 1339-63-5 (Ubiquinone)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171004
[Lr] Data última revisão:
171004
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


  8 / 1686 MEDLINE  
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[PMID]:27750036
[Au] Autor:Rodríguez-Sánchez L; Rial E
[Ad] Endereço:Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas - CSIC, Madrid, Spain.
[Ti] Título:The distinct bioenergetic properties of the human UCP1.
[So] Source:Biochimie;134:51-55, 2017 Mar.
[Is] ISSN:1638-6183
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:The uncoupling protein UCP1 from brown adipose tissue is a mitochondrial carrier which allows dissipation of metabolic energy as heat. We have characterized the human UCP1 (HsUCP1) recombinantly expressed in Saccharomyces cerevisiae and we demonstrate that HsUCP1 is activated by fatty acids and retinoids in a nucleotide sensitive manner just as its rodent orthologs. However, in the absence of regulators, rodent UCP1 presents a high ohmic proton conductance that cannot be detected in HsUCP1. Since the human protein can be activated in a nucleotide sensitive manner, we conclude that it must have lost selectively the basal proton conductance.
[Mh] Termos MeSH primário: Cardiolipinas/metabolismo
Ácidos Graxos/metabolismo
Mitocôndrias/metabolismo
Prótons
Proteína Desacopladora 1/química
[Mh] Termos MeSH secundário: Animais
Regulação da Expressão Gênica
Seres Humanos
Transporte de Íons
Potencial da Membrana Mitocondrial
Camundongos
Mitocôndrias/genética
Modelos Moleculares
Nucleotídeos de Purina/metabolismo
Ratos
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Retinoides/metabolismo
Saccharomyces cerevisiae/genética
Saccharomyces cerevisiae/metabolismo
Especificidade da Espécie
Proteína Desacopladora 1/genética
Proteína Desacopladora 1/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cardiolipins); 0 (Fatty Acids); 0 (Protons); 0 (Purine Nucleotides); 0 (Recombinant Proteins); 0 (Retinoids); 0 (UCP1 protein, human); 0 (Uncoupling Protein 1)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170216
[Lr] Data última revisão:
170216
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161023
[St] Status:MEDLINE


  9 / 1686 MEDLINE  
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[PMID]:27906631
[Au] Autor:Wang L
[Ad] Endereço:a Department of Anatomy, Physiology and Biochemistry , Swedish University of Agricultural Sciences , Uppsala , Sweden.
[Ti] Título:Mitochondrial purine and pyrimidine metabolism and beyond.
[So] Source:Nucleosides Nucleotides Nucleic Acids;35(10-12):578-594, 2016 Dec.
[Is] ISSN:1532-2335
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Carefully balanced deoxynucleoside triphosphate (dNTP) pools are essential for both nuclear and mitochondrial genome replication and repair. Two synthetic pathways operate in cells to produce dNTPs, e.g., the de novo and the salvage pathways. The key regulatory enzymes for de novo synthesis are ribonucleotide reductase (RNR) and thymidylate synthase (TS), and this process is considered to be cytosolic. The salvage pathway operates both in the cytosol (TK1 and dCK) and the mitochondria (TK2 and dGK). Mitochondrial dNTP pools are separated from the cytosolic ones owing to the double membrane structure of the mitochondria, and are formed by the salvage enzymes TK2 and dGK together with NMPKs and NDPK in postmitotic tissues, while in proliferating cells the mitochondrial dNTPs are mainly imported from the cytosol produced by the cytosolic pathways. Imbalanced mitochondrial dNTP pools lead to mtDNA depletion and/or deletions resulting in serious mitochondrial diseases. The mtDNA depletion syndrome is caused by deficiencies not only in enzymes in dNTP synthesis (TK2, dGK, p53R2, and TP) and mtDNA replication (mtDNA polymerase and twinkle helicase), but also in enzymes in other metabolic pathways such as SUCLA2 and SUCLG1, ABAT and MPV17. Basic questions are why defects in these enzymes affect dNTP synthesis and how important is mitochondrial nucleotide synthesis in the whole cell/organism perspective? This review will focus on recent studies on purine and pyrimidine metabolism, which have revealed several important links that connect mitochondrial nucleotide metabolism with amino acids, glucose, and fatty acid metabolism.
[Mh] Termos MeSH primário: Nucleotídeos de Purina/biossíntese
Erros Inatos do Metabolismo da Purina-Pirimidina/metabolismo
Nucleotídeos de Pirimidina/biossíntese
[Mh] Termos MeSH secundário: Animais
Vias Biossintéticas
Replicação do DNA
DNA Mitocondrial/biossíntese
DNA Mitocondrial/genética
Seres Humanos
Mitocôndrias/metabolismo
Estresse Oxidativo
Erros Inatos do Metabolismo da Purina-Pirimidina/tratamento farmacológico
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (DNA, Mitochondrial); 0 (Purine Nucleotides); 0 (Pyrimidine Nucleotides)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170317
[Lr] Data última revisão:
170317
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161202
[St] Status:MEDLINE


  10 / 1686 MEDLINE  
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[PMID]:27712885
[Au] Autor:Arase S; Horie K; Kato T; Noda A; Mito Y; Takahashi M; Yanagisawa T
[Ad] Endereço:Eisai Co., Ltd., Formulation Research, Pharmaceutical Science & Technology Core Function Unit, Medicine Development Center, Kawashima, Kakamigahara, Gifu 501-6195, Japan.
[Ti] Título:Intelligent peak deconvolution through in-depth study of the data matrix from liquid chromatography coupled with a photo-diode array detector applied to pharmaceutical analysis.
[So] Source:J Chromatogr A;1469:35-47, 2016 Oct 21.
[Is] ISSN:1873-3778
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Multivariate curve resolution-alternating least squares (MCR-ALS) method was investigated for its potential to accelerate pharmaceutical research and development. The fast and efficient separation of complex mixtures consisting of multiple components, including impurities as well as major drug substances, remains a challenging application for liquid chromatography in the field of pharmaceutical analysis. In this paper we suggest an integrated analysis algorithm functioning on a matrix of data generated from HPLC coupled with photo-diode array detector (HPLC-PDA) and consisting of the mathematical program for the developed multivariate curve resolution method using an expectation maximization (EM) algorithm with a bidirectional exponentially modified Gaussian (BEMG) model function as a constraint for chromatograms and numerous PDA spectra aligned with time axis. The algorithm provided less than ±1.0% error between true and separated peak area values at resolution (R ) of 0.6 using simulation data for a three-component mixture with an elution order of a/b/c with similarity (a/b)=0.8410, (b/c)=0.9123 and (a/c)=0.9809 of spectra at peak apex. This software concept provides fast and robust separation analysis even when method development efforts fail to achieve complete separation of the target peaks. Additionally, this approach is potentially applicable to peak deconvolution, allowing quantitative analysis of co-eluted compounds having exactly the same molecular weight. This is complementary to the use of LC-MS to perform quantitative analysis on co-eluted compounds using selected ions to differentiate the proportion of response attributable to each compound.
[Mh] Termos MeSH primário: Preparações Farmacêuticas/análise
[Mh] Termos MeSH secundário: Acetofenonas/análise
Benzofenonas/análise
Butanos/análise
Cromatografia Líquida de Alta Pressão/instrumentação
Cromatografia Líquida de Alta Pressão/métodos
Citidina/análise
Fluorbenzenos/análise
Isomerismo
Cetonas/análise
Análise dos Mínimos Quadrados
Espectrometria de Massas
Peso Molecular
Análise Multivariada
Nucleotídeos de Purina/análise
Uracila/análise
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Acetophenones); 0 (Benzophenones); 0 (Butanes); 0 (Fluorobenzenes); 0 (Ketones); 0 (Pharmaceutical Preparations); 0 (Purine Nucleotides); 56HH86ZVCT (Uracil); 5CSZ8459RP (Cytidine); 88BNC11B9C (4,4'-difluorobenzophenone); F27Q043NT1 (valerophenone)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161008
[St] Status:MEDLINE



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