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[PMID]:28454702
[Au] Autor:Ellery SJ; Della Gatta PA; Bruce CR; Kowalski GM; Davies-Tuck M; Mockler JC; Murthi P; Walker DW; Snow RJ; Dickinson H
[Ad] Endereço:The Ritchie Centre, Hudson Institute of Medical Research, Department of Obstetrics and Gynaecology, Monash University, Melbourne, Australia.
[Ti] Título:Creatine biosynthesis and transport by the term human placenta.
[So] Source:Placenta;52:86-93, 2017 Apr.
[Is] ISSN:1532-3102
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Creatine is an amino acid derivative that is involved in preserving ATP homeostasis. Previous studies suggest an important role for the creatine kinase circuit for placental ATP turnover. Creatine is obtained from both the diet and endogenous synthesis, usually along the renal-hepatic axis. However, some tissues with a high-energy demand have an inherent capacity to synthesise creatine. In this study, we determined if the term human placenta has the enzymatic machinary to synthesise creatine. METHODS: Eleven placentae were collected following elective term caesarean section. Samples from the 4 quadrants of each placenta were either fixed in formalin or frozen. qPCR was used to determine the mRNA expression of the creatine synthesising enzymes arginine:glycine amidinotransferase (AGAT) and guanidinoacetate methyltransferase (GAMT), and the creatine transporter (SLC6A8). Protein expression of AGAT and GAMT was quantified by Western blot, and observations of cell localisation of AGAT, GAMT and SLC6A8 made with immunohistochemistry. Synthesis of guanidinoacetate (GAA; creatine precursor) and creatine in placental homogenates was determined via GC-MS and HPLC, respectively. RESULTS: AGAT, GAMT and SLC6A8 mRNA and protein were detected in the human placenta. AGAT staining was identified in stromal and endothelial cells of the fetal capillaries. GAMT and SLC6A8 staining was localised to the syncytiotrophoblast of the fetal villi. Ex vivo, tissue homogenates produce both GAA (4.6 nmol mg protein h ) and creatine (52.8 nmol mg protein h ). DISCUSSION: The term human placenta has the capacity to synthesise creatine. These data present a new understanding of placental energy metabolism.
[Mh] Termos MeSH primário: Amidinotransferases/metabolismo
Creatina/metabolismo
Guanidinoacetato N-Metiltransferase/metabolismo
Proteínas de Membrana Transportadoras/metabolismo
Placenta/metabolismo
[Mh] Termos MeSH secundário: Transporte Biológico
Creatina/biossíntese
Células Endoteliais/metabolismo
Metabolismo Energético/fisiologia
Feminino
Seres Humanos
Gravidez
Células Estromais/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Membrane Transport Proteins); 0 (creatine transporter); EC 2.1.1.2 (GAMT protein, human); EC 2.1.1.2 (Guanidinoacetate N-Methyltransferase); EC 2.1.4.- (Amidinotransferases); EC 2.1.4.1 (glycine amidinotransferase); MU72812GK0 (Creatine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


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[PMID]:27802572
[Au] Autor:Mei X; Alvarez J; Bon Ramos A; Samanta U; Iwata-Reuyl D; Swairjo MA
[Ad] Endereço:Department of Chemistry and Biochemistry, San Diego State University- 5500 Campanile Drive, San Diego, California, 92182.
[Ti] Título:Crystal structure of the archaeosine synthase QueF-like-Insights into amidino transfer and tRNA recognition by the tunnel fold.
[So] Source:Proteins;85(1):103-116, 2017 Jan.
[Is] ISSN:1097-0134
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The tunneling-fold (T-fold) structural superfamily has emerged as a versatile protein scaffold of diverse catalytic activities. This is especially evident in the pathways to the 7-deazaguanosine modified nucleosides of tRNA queuosine and archaeosine. Four members of the T-fold superfamily have been confirmed in these pathways and here we report the crystal structure of a fifth enzyme; the recently discovered amidinotransferase QueF-Like (QueF-L), responsible for the final step in the biosynthesis of archaeosine in the D-loop of tRNA in a subset of Crenarchaeota. QueF-L catalyzes the conversion of the nitrile group of the 7-cyano-7-deazaguanine (preQ ) base of preQ -modified tRNA to a formamidino group. The structure, determined in the presence of preQ , reveals a symmetric T-fold homodecamer of two head-to-head facing pentameric subunits, with 10 active sites at the inter-monomer interfaces. Bound preQ forms a stable covalent thioimide bond with a conserved active site cysteine similar to the intermediate previously observed in the nitrile reductase QueF. Despite distinct catalytic functions, phylogenetic distributions, and only 19% sequence identity, the two enzymes share a common preQ binding pocket, and likely a common mechanism of thioimide formation. However, due to tight twisting of its decamer, QueF-L lacks the NADPH binding site present in QueF. A large positively charged molecular surface and a docking model suggest simultaneous binding of multiple tRNA molecules and structure-specific recognition of the D-loop by a surface groove. The structure sheds light on the mechanism of nitrile amidation, and the evolution of diverse chemistries in a common fold. Proteins 2016; 85:103-116. © 2016 Wiley Periodicals, Inc.
[Mh] Termos MeSH primário: Amidinotransferases/química
Proteínas Arqueais/química
Guanosina/análogos & derivados
Pirimidinonas/química
Pyrobaculum/enzimologia
Pirróis/química
Processamento Pós-Transcricional do RNA
[Mh] Termos MeSH secundário: Amidinotransferases/genética
Amidinotransferases/metabolismo
Sequência de Aminoácidos
Proteínas Arqueais/genética
Proteínas Arqueais/metabolismo
Domínio Catalítico
Clonagem Molecular
Cristalografia por Raios X
Escherichia coli/genética
Escherichia coli/metabolismo
Expressão Gênica
Guanosina/química
Guanosina/metabolismo
Simulação de Acoplamento Molecular
Ligação Proteica
Conformação Proteica em alfa-Hélice
Conformação Proteica em Folha beta
Domínios e Motivos de Interação entre Proteínas
Multimerização Proteica
Subunidades Proteicas/química
Subunidades Proteicas/genética
Subunidades Proteicas/metabolismo
Pirimidinonas/metabolismo
Pyrobaculum/genética
Pirróis/metabolismo
RNA Arqueal/química
RNA Arqueal/genética
RNA Arqueal/metabolismo
RNA de Transferência/química
RNA de Transferência/genética
RNA de Transferência/metabolismo
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Alinhamento de Sequência
Homologia de Sequência de Aminoácidos
Especificidade por Substrato
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (2-amino-5-cyanopyrrolo(2,3-d)pyrimidin-4-one); 0 (Archaeal Proteins); 0 (Protein Subunits); 0 (Pyrimidinones); 0 (Pyrroles); 0 (RNA, Archaeal); 0 (Recombinant Proteins); 12133JR80S (Guanosine); 148608-52-0 (archaeosine); 9014-25-9 (RNA, Transfer); EC 2.1.4.- (Amidinotransferases)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170724
[Lr] Data última revisão:
170724
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161102
[St] Status:MEDLINE
[do] DOI:10.1002/prot.25202


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[PMID]:27784962
[Au] Autor:Osna NA; Feng D; Ganesan M; Maillacheruvu PF; Orlicky DJ; French SW; Tuma DJ; Kharbanda KK
[Ad] Endereço:Natalia A Osna, Dan Feng, Murali Ganesan, Dean J Tuma, Kusum K Kharbanda, Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, NE 68105, United States.
[Ti] Título:Prolonged feeding with guanidinoacetate, a methyl group consumer, exacerbates ethanol-induced liver injury.
[So] Source:World J Gastroenterol;22(38):8497-8508, 2016 Oct 14.
[Is] ISSN:2219-2840
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:AIM: To investigate the hypothesis that exposure to guanidinoacetate (GAA, a potent methyl-group consumer) either alone or combined with ethanol intake for a prolonged period of time would cause more advanced liver pathology thus identifying methylation defects as the initiator and stimulator for progressive liver damage. METHODS: Adult male Wistar rats were fed the control or ethanol Lieber DeCarli diet in the absence or presence of GAA supplementation. At the end of 6 wk of the feeding regimen, various biochemical and histological analyses were conducted. RESULTS: Contrary to our expectations, we observed that GAA treatment alone resulted in a histologically normal liver without evidence of hepatosteatosis despite persistence of some abnormal biochemical parameters. This protection could result from the generation of creatine from the ingested GAA. Ethanol treatment for 6 wk exhibited changes in liver methionine metabolism and persistence of histological and biochemical defects as reported before. Further, when the rats were fed the GAA-supplemented ethanol diet, similar histological and biochemical changes as observed after 2 wk of combined treatment, including inflammation, macro- and micro-vesicular steatosis and a marked decrease in the methylation index were noted. In addition, rats on the combined treatment exhibited increased liver toxicity and even early fibrotic changes in a subset of animals in this group. The worsening liver pathology could be related to the profound reduction in the hepatic methylation index, an increased accumulation of GAA and the inability of creatine generated to exert its hepato-protective effects in the setting of ethanol. CONCLUSION: To conclude, prolonged exposure to a methyl consumer superimposed on chronic ethanol consumption causes persistent and pronounced liver damage.
[Mh] Termos MeSH primário: Etanol/efeitos adversos
Glicina/análogos & derivados
Hepatopatias/fisiopatologia
[Mh] Termos MeSH secundário: Alanina Transaminase/sangue
Amidinotransferases/metabolismo
Animais
Aspartato Aminotransferases/sangue
Peso Corporal
Proteínas de Ligação ao Cálcio/metabolismo
Colesterol/química
Proteínas de Ligação a DNA/metabolismo
Suplementos Nutricionais
Etanol/administração & dosagem
Ácidos Graxos/química
Fígado Gorduroso
Glicina/administração & dosagem
Guanidinoacetato N-Metiltransferase/metabolismo
Homocisteína/sangue
Inflamação
Insulina/química
Fígado/fisiopatologia
Masculino
Proteínas do Tecido Nervoso/metabolismo
Complexo de Endopeptidases do Proteassoma/metabolismo
Ratos
Ratos Wistar
S-Adenosil-Homocisteína/química
S-Adenosilmetionina/química
Triglicerídeos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Calcium-Binding Proteins); 0 (DNA-Binding Proteins); 0 (Fatty Acids); 0 (Insulin); 0 (Nerve Tissue Proteins); 0 (Triglycerides); 0 (nucleobindin); 0LVT1QZ0BA (Homocysteine); 3K9958V90M (Ethanol); 7LP2MPO46S (S-Adenosylmethionine); 979-92-0 (S-Adenosylhomocysteine); 97C5T2UQ7J (Cholesterol); EC 2.1.1.2 (Gamt protein, rat); EC 2.1.1.2 (Guanidinoacetate N-Methyltransferase); EC 2.1.4.- (Amidinotransferases); EC 2.1.4.1 (glycine amidinotransferase); EC 2.6.1.1 (Aspartate Aminotransferases); EC 2.6.1.2 (Alanine Transaminase); EC 3.4.25.1 (Proteasome Endopeptidase Complex); GO52O1A04E (glycocyamine); TE7660XO1C (Glycine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170627
[Lr] Data última revisão:
170627
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161028
[St] Status:MEDLINE


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[PMID]:27581622
[Au] Autor:Ganesan M; Feng D; Barton RW; Thomes PG; McVicker BL; Tuma DJ; Osna NA; Kharbanda KK
[Ad] Endereço:Research Service, Veterans Affairs Nebraska-Western Iowa Health Care System, Omaha, Nebraska.
[Ti] Título:Creatine Supplementation Does Not Prevent the Development of Alcoholic Steatosis.
[So] Source:Alcohol Clin Exp Res;40(11):2312-2319, 2016 Nov.
[Is] ISSN:1530-0277
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Alcohol-induced reduction in the hepatocellular S-adenosylmethionine (SAM):S-adenosylhomocysteine (SAH) ratio impairs the activities of many SAM-dependent methyltransferases. These impairments ultimately lead to the generation of several hallmark features of alcoholic liver injury including steatosis. Guanidinoacetate methyltransferase (GAMT) is an important enzyme that catalyzes the final reaction in the creatine biosynthetic process. The liver is a major site for creatine synthesis which places a substantial methylation burden on this organ as GAMT-mediated reactions consume as much as 40% of all the SAM-derived methyl groups. We hypothesized that dietary creatine supplementation could potentially spare SAM, preserve the hepatocellular SAM:SAH ratio, and thereby prevent the development of alcoholic steatosis and other consequences of impaired methylation reactions. METHODS: For these studies, male Wistar rats were pair-fed the Lieber-DeCarli control or ethanol (EtOH) diet with or without 1% creatine supplementation. At the end of 4 to 5 weeks of feeding, relevant biochemical and histological analyses were performed. RESULTS: We observed that creatine supplementation neither prevented alcoholic steatosis nor attenuated the alcohol-induced impairments in proteasome activity. The lower hepatocellular SAM:SAH ratio seen in the EtOH-fed rats was also not normalized or SAM levels spared when these rats were fed the creatine-supplemented EtOH diet. However, a >10-fold increased level of creatine was observed in the liver, serum, and hearts of rats fed the creatine-supplemented diets. CONCLUSIONS: Overall, dietary creatine supplementation did not prevent alcoholic liver injury despite its known efficacy in preventing high-fat-diet-induced steatosis. Betaine, a promethylating agent that maintains the hepatocellular SAM:SAH, still remains our best option for treating alcoholic steatosis.
[Mh] Termos MeSH primário: Creatina/uso terapêutico
Fígado Gorduroso Alcoólico/prevenção & controle
[Mh] Termos MeSH secundário: Amidinotransferases/metabolismo
Animais
Suplementos Nutricionais
Guanidinoacetato N-Metiltransferase/metabolismo
Rim/enzimologia
Fígado/enzimologia
Masculino
Miocárdio/metabolismo
Ratos Wistar
S-Adenosil-Homocisteína/metabolismo
S-Adenosilmetionina/metabolismo
[Pt] Tipo de publicação:EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
7LP2MPO46S (S-Adenosylmethionine); 979-92-0 (S-Adenosylhomocysteine); EC 2.1.1.2 (Guanidinoacetate N-Methyltransferase); EC 2.1.4.- (Amidinotransferases); EC 2.1.4.1 (glycine amidinotransferase); MU72812GK0 (Creatine)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170621
[Lr] Data última revisão:
170621
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160902
[St] Status:MEDLINE
[do] DOI:10.1111/acer.13214


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[PMID]:27289319
[Au] Autor:Ogasawara Y; Fujimori M; Kawata J; Dairi T
[Ad] Endereço:Graduate School of Engineering, Hokkaido University, N 13 W 8, Kita-ku, Sapporo, Hokkaido 060-8628, Japan. Electronic address: yogasawa@eng.hokudai.ac.jp.
[Ti] Título:Characterization of three amidinotransferases involved in the biosynthesis of ketomemicins.
[So] Source:Bioorg Med Chem Lett;26(15):3662-4, 2016 08 01.
[Is] ISSN:1464-3405
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:We recently reported a novel class of amide bond forming enzymes (peptide ligases) involved in the biosynthesis of pheganomycins, resorcinomycins and ketomemicins. This class of enzymes exclusively utilizes Nα-amidino amino acids as the N-terminal substrate. In this Letter, we characterized three new amidinotransferases involved in the biosynthesis of ketomemicins and showed that l-arginine was the amidino-acceptor of amidinotransferases in both the Micromonospora sp. and Streptomyces mobaraensis clusters, while the Salinispora tropica enzyme recognized l-valine. Unexpectedly, the S. tropica enzyme accepted several different amino acids as amidino acceptors in addition to l-valine. Accordingly, we re-investigated the specific metabolites governed by the gene cluster of S. tropica and identified several minor congeners of ketomemicin C with different N-terminal amidino-amino acids. These results indicate that the amidinotransferase of S. tropica is promiscuous and could be useful to generate new ketomemicin-type natural products.
[Mh] Termos MeSH primário: Amidinotransferases/metabolismo
Produtos Biológicos/metabolismo
Oligopeptídeos/biossíntese
[Mh] Termos MeSH secundário: Amidinotransferases/química
Produtos Biológicos/química
Estrutura Molecular
Oligopeptídeos/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Biological Products); 0 (Oligopeptides); EC 2.1.4.- (Amidinotransferases)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171122
[Lr] Data última revisão:
171122
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160613
[St] Status:MEDLINE


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[PMID]:27001789
[Au] Autor:Koshoridze N; Kuchukashvili Z; Menabde K; Lekiashvili Sh; Koshoridze M
[Ad] Endereço:I. Javakhishvili Tbilisi State University, Faculty of Exact and Natural Sciences, Department of Biology, Georgia.
[Ti] Título:ALTERATIONS IN BRAIN CREATINE CONCENTRATIONS UNDER LONG-TERM SOCIAL ISOLATION (EXPERIMENTAL STUDY).
[So] Source:Georgian Med News;(251):70-7, 2016 Feb.
[Is] ISSN:1512-0112
[Cp] País de publicação:Georgia (Republic)
[La] Idioma:eng
[Ab] Resumo:Stress represents one of the main problems of modern humanity. This study was done for understanding more clearly alterations in creatine content of the brain under psycho-emotional stress induced by long-term social isolation. It was shown that under 30 days social isolation creatine amount in the brain was arisen, while decreasing concentrations of synthesizing enzymes (AGAT, GAMT) and creatine transporter protein (CrT). Another important point was that such changes were accompanied by down-regulation of creatine kinase (CK), therefore the enzyme's concentration was lowered. In addition, it was observed that content of phosphocreatine (PCr) and ATP were also reduced, thus indicating down-regulation of energy metabolism of brain that is really a crucial point for its normal functioning. To sum up the results it can be underlined that long-term social isolation has negative influence on energy metabolism of brain; and as a result reduce ATP content, while increase of free creatine concentration, supposedly maintaining maximal balance for ATP amount, but here must be also noted that up-regulated oxidative pathways might have impact on blood brain barrier, resulting on its permeability.
[Mh] Termos MeSH primário: Encéfalo/metabolismo
Creatina/metabolismo
Isolamento Social
[Mh] Termos MeSH secundário: Trifosfato de Adenosina/metabolismo
Amidinotransferases/metabolismo
Animais
Creatina Quinase/metabolismo
Metabolismo Energético
Guanidinoacetato N-Metiltransferase/metabolismo
Masculino
Proteínas de Membrana Transportadoras/metabolismo
Fosfocreatina/metabolismo
Ratos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Membrane Transport Proteins); 0 (creatine transporter); 020IUV4N33 (Phosphocreatine); 8L70Q75FXE (Adenosine Triphosphate); EC 2.1.1.2 (Gamt protein, rat); EC 2.1.1.2 (Guanidinoacetate N-Methyltransferase); EC 2.1.4.- (Amidinotransferases); EC 2.1.4.1 (glycine amidinotransferase); EC 2.7.3.2 (Creatine Kinase); MU72812GK0 (Creatine)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:160322
[Lr] Data última revisão:
160322
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160323
[St] Status:MEDLINE


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[PMID]:26928755
[Au] Autor:Terlemez S; Demir F; Bulut Y; Carti Ö; Gökdogan D; Tokgöz Y; Yenigün A
[Ad] Endereço:Pediatric Cardiology department, Adnan Menderes University Medicine Faculty, Aydin, Turkey. semihaterlemez@yahoo.com.
[Ti] Título:DRESS syndrome developed related to acetylsalicylic acid use.
[So] Source:Pediatr Allergy Immunol;27(2):227-30, 2016 Mar.
[Is] ISSN:1399-3038
[Cp] País de publicação:England
[La] Idioma:eng
[Mh] Termos MeSH primário: Aspirina/efeitos adversos
Síndrome de Hipersensibilidade a Medicamentos/diagnóstico
Eosinófilos/fisiologia
Linfócitos/patologia
Febre Reumática/tratamento farmacológico
[Mh] Termos MeSH secundário: Amidinotransferases/sangue
Aspirina/uso terapêutico
Criança
Síndrome de Hipersensibilidade a Medicamentos/etiologia
Diagnóstico Precoce
Feminino
Seres Humanos
Febre Reumática/complicações
Febre Reumática/diagnóstico
[Pt] Tipo de publicação:LETTER
[Nm] Nome de substância:
EC 2.1.4.- (Amidinotransferases); R16CO5Y76E (Aspirin)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160302
[St] Status:MEDLINE
[do] DOI:10.1111/pai.12484


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[PMID]:26729229
[Au] Autor:Khan A; Tian L; Zhang C; Yuan K; Xu S
[Ad] Endereço:Chinese Academy of Sciences (CAS) Key Laboratory of Computational Biology, Max Planck Independent Research Group on Population Genomics, CAS-MPG Partner Institute for Computational Biology (PICB), Shanghai Institutes for Biological Sciences, Chinese academy of Sciences, Shanghai 200031, China.
[Ti] Título:Genetic diversity and natural selection footprints of the glycine amidinotransferase gene in various human populations.
[So] Source:Sci Rep;6:18755, 2016 Jan 05.
[Is] ISSN:2045-2322
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The glycine amidinotransferase gene (GATM) plays a vital role in energy metabolism in muscle tissues and is associated with multiple clinically important phenotypes. However, the genetic diversity of the GATM gene remains poorly understood within and between human populations. Here we analyzed the 1,000 Genomes Project data through population genetics approaches and observed significant genetic diversity across the GATM gene among various continental human populations. We observed considerable variations in GATM allele frequencies and haplotype composition among different populations. Substantial genetic differences were observed between East Asian and European populations (FST = 0.56). In addition, the frequency of a distinct major GATM haplotype in these groups was congruent with population-wide diversity at this locus. Furthermore, we identified GATM as the top differentiated gene compared to the other statin drug response-associated genes. Composite multiple analyses identified signatures of positive selection at the GATM locus, which was estimated to have occurred around 850 generations ago in European populations. As GATM catalyzes the key step of creatine biosynthesis involved in energy metabolism, we speculate that the European prehistorical demographic transition from hunter-gatherer to farming cultures was the driving force of selection that fulfilled creatine-based metabolic requirement of the populations.
[Mh] Termos MeSH primário: Amidinotransferases/genética
Variação Genética
Genética Populacional
Seleção Genética
[Mh] Termos MeSH secundário: Grupos de Populações Continentais/genética
Loci Gênicos
Genoma Humano
Estudo de Associação Genômica Ampla
Haplótipos
Seres Humanos
Desequilíbrio de Ligação
Característica Quantitativa Herdável
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
EC 2.1.4.- (Amidinotransferases); EC 2.1.4.1 (glycine amidinotransferase)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160106
[St] Status:MEDLINE
[do] DOI:10.1038/srep18755


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[PMID]:26542286
[Au] Autor:Joncquel-Chevalier Curt M; Voicu PM; Fontaine M; Dessein AF; Porchet N; Mention-Mulliez K; Dobbelaere D; Soto-Ares G; Cheillan D; Vamecq J
[Ad] Endereço:Biochemistry and Molecular Biology, Hormonology-Metabolism-Nutrition & Oncology (HMNO), Center of Biology & Pathology (CBP) Pierre-Marie Degand, CHRU Lille, 59037 Lille, France; RADEME Research Team for Rare Metabolic and Developmental Diseases, EA 7364, Université Lille 2, Lille, France.
[Ti] Título:Creatine biosynthesis and transport in health and disease.
[So] Source:Biochimie;119:146-65, 2015 Dec.
[Is] ISSN:1638-6183
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Creatine is physiologically provided equally by diet and by endogenous synthesis from arginine and glycine with successive involvements of arginine glycine amidinotransferase [AGAT] and guanidinoacetate methyl transferase [GAMT]. A specific plasma membrane transporter, creatine transporter [CRTR] (SLC6A8), further enables cells to incorporate creatine and through uptake of its precursor, guanidinoacetate, also directly contributes to creatine biosynthesis. Breakthrough in the role of creatine has arisen from studies on creatine deficiency disorders. Primary creatine disorders are inherited as autosomal recessive (mutations affecting GATM [for glycine-amidinotransferase, mitochondrial]) and GAMT genes) or X-linked (SLC6A8 gene) traits. They have highlighted the role of creatine in brain functions altered in patients (global developmental delay, intellectual disability, behavioral disorders). Creatine modulates GABAergic and glutamatergic cerebral pathways, presynaptic CRTR (SLC6A8) ensuring re-uptake of synaptic creatine. Secondary creatine disorders, addressing other genes, have stressed the extraordinary imbrication of creatine metabolism with many other cellular pathways. This high dependence on multiple pathways supports creatine as a cellular sensor, to cell methylation and energy status. Creatine biosynthesis consumes 40% of methyl groups produced as S-adenosylmethionine, and creatine uptake is controlled by AMP activated protein kinase, a ubiquitous sensor of energy depletion. Today, creatine is considered as a potential sensor of cell methylation and energy status, a neurotransmitter influencing key (GABAergic and glutamatergic) CNS neurotransmission, therapeutic agent with anaplerotic properties (towards creatine kinases [creatine-creatine phosphate cycle] and creatine neurotransmission), energetic and antioxidant compound (benefits in degenerative diseases through protection against energy depletion and oxidant species) with osmolyte behavior (retention of water by muscle). This review encompasses all these aspects by providing an illustrated metabolic account for brain and body creatine in health and disease, an algorithm to diagnose metabolic and gene bases of primary and secondary creatine deficiencies, and a metabolic exploration by (1)H-MRS assessment of cerebral creatine levels and response to therapeutic measures.
[Mh] Termos MeSH primário: Amidinotransferases/metabolismo
Creatina/metabolismo
Guanidinoacetato N-Metiltransferase/metabolismo
Proteínas do Tecido Nervoso/metabolismo
Proteínas da Membrana Plasmática de Transporte de Neurotransmissores/metabolismo
[Mh] Termos MeSH secundário: Proteínas Quinases Ativadas por AMP/metabolismo
Amidinotransferases/deficiência
Amidinotransferases/genética
Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico
Erros Inatos do Metabolismo dos Aminoácidos/enzimologia
Erros Inatos do Metabolismo dos Aminoácidos/genética
Erros Inatos do Metabolismo dos Aminoácidos/metabolismo
Sistemas de Transporte de Aminoácidos Básicos/deficiência
Sistemas de Transporte de Aminoácidos Básicos/genética
Sistemas de Transporte de Aminoácidos Básicos/metabolismo
Animais
Transporte Biológico Ativo
Encefalopatias Metabólicas Congênitas/diagnóstico
Encefalopatias Metabólicas Congênitas/enzimologia
Encefalopatias Metabólicas Congênitas/genética
Encefalopatias Metabólicas Congênitas/metabolismo
Creatina/biossíntese
Creatina/deficiência
Creatina/genética
Deficiências do Desenvolvimento/diagnóstico
Deficiências do Desenvolvimento/enzimologia
Deficiências do Desenvolvimento/genética
Deficiências do Desenvolvimento/metabolismo
Metabolismo Energético
Guanidinoacetato N-Metiltransferase/deficiência
Guanidinoacetato N-Metiltransferase/genética
Atrofia Girata/diagnóstico
Atrofia Girata/enzimologia
Atrofia Girata/genética
Atrofia Girata/metabolismo
Seres Humanos
Hiperamonemia/diagnóstico
Hiperamonemia/enzimologia
Hiperamonemia/genética
Hiperamonemia/metabolismo
Deficiência Intelectual/diagnóstico
Deficiência Intelectual/enzimologia
Deficiência Intelectual/genética
Deficiência Intelectual/metabolismo
Transtornos do Desenvolvimento da Linguagem/diagnóstico
Transtornos do Desenvolvimento da Linguagem/enzimologia
Transtornos do Desenvolvimento da Linguagem/genética
Transtornos do Desenvolvimento da Linguagem/metabolismo
Retardo Mental Ligado ao Cromossomo X/diagnóstico
Retardo Mental Ligado ao Cromossomo X/enzimologia
Retardo Mental Ligado ao Cromossomo X/genética
Retardo Mental Ligado ao Cromossomo X/metabolismo
Metilação
Transtornos dos Movimentos/congênito
Transtornos dos Movimentos/diagnóstico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (Amino Acid Transport Systems, Basic); 0 (Nerve Tissue Proteins); 0 (Plasma Membrane Neurotransmitter Transport Proteins); 0 (SLC25A15 protein, human); 0 (SLC6A8 protein, human); 7LP2MPO46S (S-Adenosylmethionine); E524N2IXA3 (Ornithine); EC 2.1.1.2 (GAMT protein, human); EC 2.1.1.2 (Guanidinoacetate N-Methyltransferase); EC 2.1.4.- (Amidinotransferases); EC 2.1.4.1 (glycine amidinotransferase); EC 2.7.11.31 (AMP-Activated Protein Kinases); MU72812GK0 (Creatine)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151107
[St] Status:MEDLINE


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[PMID]:26490222
[Au] Autor:Stockler-Ipsiroglu S; Apatean D; Battini R; DeBrosse S; Dessoffy K; Edvardson S; Eichler F; Johnston K; Koeller DM; Nouioua S; Tazir M; Verma A; Dowling MD; Wierenga KJ; Wierenga AM; Zhang V; Wong LJ
[Ad] Endereço:Division of Biochemical Diseases, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada; Child & Family Research Institute, BC Children's Hospital, Vancouver, BC, Canada. Electronic address: sstockler@cw.bc.ca.
[Ti] Título:Arginine:glycine amidinotransferase (AGAT) deficiency: Clinical features and long term outcomes in 16 patients diagnosed worldwide.
[So] Source:Mol Genet Metab;116(4):252-9, 2015 Dec.
[Is] ISSN:1096-7206
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Arginine:glycine aminotransferase (AGAT) (GATM) deficiency is an autosomal recessive inborn error of creative synthesis. OBJECTIVE: We performed an international survey among physicians known to treat patients with AGAT deficiency, to assess clinical characteristics and long-term outcomes of this ultra-rare condition. RESULTS: 16 patients from 8 families of 8 different ethnic backgrounds were included. 1 patient was asymptomatic when diagnosed at age 3 weeks. 15 patients diagnosed between 16 months and 25 years of life had intellectual disability/developmental delay (IDD). 8 patients also had myopathy/proximal muscle weakness. Common biochemical denominators were low/undetectable guanidinoacetate (GAA) concentrations in urine and plasma, and low/undetectable cerebral creatine levels. 3 families had protein truncation/null mutations. The rest had missense and splice mutations. Treatment with creatine monohydrate (100-800 mg/kg/day) resulted in almost complete restoration of brain creatine levels and significant improvement of myopathy. The 2 patients treated since age 4 and 16 months had normal cognitive and behavioral development at age 10 and 11 years. Late treated patients had limited improvement of cognitive functions. CONCLUSION: AGAT deficiency is a treatable intellectual disability. Early diagnosis may prevent IDD and myopathy. Patients with unexplained IDD with and without myopathy should be assessed for AGAT deficiency by determination of urine/plasma GAA and cerebral creatine levels (via brain MRS), and by GATM gene sequencing.
[Mh] Termos MeSH primário: Amidinotransferases/deficiência
Erros Inatos do Metabolismo dos Aminoácidos/tratamento farmacológico
Creatina/uso terapêutico
Deficiência Intelectual/tratamento farmacológico
Doenças Musculares/tratamento farmacológico
Distúrbios da Fala/tratamento farmacológico
[Mh] Termos MeSH secundário: Adolescente
Amidinotransferases/química
Amidinotransferases/genética
Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico
Erros Inatos do Metabolismo dos Aminoácidos/genética
Erros Inatos do Metabolismo dos Aminoácidos/fisiopatologia
Criança
Pré-Escolar
Creatina/deficiência
Deficiências do Desenvolvimento/diagnóstico
Deficiências do Desenvolvimento/tratamento farmacológico
Deficiências do Desenvolvimento/genética
Deficiências do Desenvolvimento/fisiopatologia
Feminino
Expressão Gênica
Genes Recessivos
Glicina/análogos & derivados
Glicina/sangue
Glicina/deficiência
Glicina/urina
Seres Humanos
Deficiência Intelectual/diagnóstico
Deficiência Intelectual/genética
Deficiência Intelectual/fisiopatologia
Espectroscopia de Ressonância Magnética
Masculino
Modelos Moleculares
Doenças Musculares/diagnóstico
Doenças Musculares/genética
Doenças Musculares/fisiopatologia
Mutação
Estrutura Secundária de Proteína
Estrutura Terciária de Proteína
Análise de Sequência de DNA
Distúrbios da Fala/diagnóstico
Distúrbios da Fala/genética
Distúrbios da Fala/fisiopatologia
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
EC 2.1.4.- (Amidinotransferases); EC 2.1.4.1 (glycine amidinotransferase); GO52O1A04E (glycocyamine); MU72812GK0 (Creatine); TE7660XO1C (Glycine)
[Em] Mês de entrada:1609
[Cu] Atualização por classe:151222
[Lr] Data última revisão:
151222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151023
[St] Status:MEDLINE



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