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Palythine-threonine, a major novel mycosporine-like amino acid (MAA) isolated from the hermatypic coral Pocillopora capitata

CARIGNAN, Mario O.; CARDOZO, Karina H. M.; OLIVEIRA-SILVA, Diogo; COLEPICOLO, Pio; CARRETO, Jose I.
Fonte: ELSEVIER SCIENCE SA Publicador: ELSEVIER SCIENCE SA
Tipo: Artigo de Revista Científica
ENG
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Using a high-resolution reverse-phase liquid chromatography method we found that the tissues of the hermatypic coral Pocillopora capitato (collected in Santiago Bay, Mexico) contain a high diversity of primary and secondary mycosporine-like amino acids (MAAs) typical of some reef-building coral species: mycosporine-glycine, shinorine, porphyra-334, mycosporine-methylamine-serine, mycosporine-methylamine-threonine, palythine-serine, palythine and one additional novel predominant MAA, with an absorbance maximum of 320 nm. Here we document the isolation and characterization of this novel MAA from the coral A capitata. Using low multi-stage mass analyses of deuterated and non deuterated compounds, high-resolution mass analyses (Time of Flight, TOF) and other techniques, this novel compound was characterized as palythine-threonine. Palythine-threonine was also present in high concentrations in the corals Pocillopora eydouxi and Stylophora pistillata indicating a wider distribution of this MAA among reef-building corals. From structural considerations we suggest that palythine-threonine is formed by decarboxylation of porphyra-334 followed by demethylation of mycosporine-methylamine-threonine. (C) 2008 Elsevier B.V. All rights reserved.; CNPq-Instituto do Milenio and Fapesp from Brazil; CNPq-Instituto do Milenio; Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); CONICET from Argentina; CONICET from Argentina[PIP 5009]; INIDEP[1535]; INIDEP

Análise do perfil de expressão de serina/treonina fosfatases e prospecção da função biológica para algumas dessas enzimas em Dictyostelium discoideum; Analysis of serine/threonine phosphatases expression profile and biological function prospection for some of these enzymes in Dictyostelium discoideum

Martins, Layla Farage
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 13/12/2010 PT
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A fosforilação reversível de proteínas em resíduos de serina e treonina, catalisada por quinases e fosfatases desempenha papel chave na regulação do crescimento e na diferenciação celular em eucariotos. As serina/treonina proteínas fosfatases (PSTPs) são atualmente divididas em três famílias denominadas PPP (PhosphoProtein Phosphatase), PPM (Phosphoprotein Phosphatase Magnesium-dependent) e FCP/SCP (RNA polymerase II CTD phosphatase), sendo que os membros da família PPP são, frequentemente, holoenzimas compostas de uma subunidade catalítica associada a uma ou mais subunidades reguladoras, as quais definem a função, localização e especificidade ao substrato da fosfatase. Neste trabalho, analisamos, através de RT-qPCR, o perfil de expressão dos genes codificadores de subunidades catalíticas de PPPs de Dictyostelium discoideum (PP1c, PP2Ac, PP4c, PP4c-like, PP6c e PP5c) e de 16 potenciais parceiros moleculares de algumas destas subunidades catalíticas, tais como DdI-2 e DdI-3, sabidamente inibidores da PP1c. Em resposta ao estresse térmico de células da fase de crescimento, detectamos o aumento dos níveis de transcritos de PP4c e PP6c e também de DdI-2, DdI-3 e DDB_G0292194, esta última, uma proteína de função desconhecida que interage com a PP1c em ensaios de duplo-híbrido em leveduras. Por outro lado...

Identificação de resíduos de treonina e tirosina importantes na regulação da atividade do receptor P2X4 humano através de mutagênese sítio-dirigida; Identification of threonine and tyrosine residues important for human P2X4 receptor activity by site-directed mutagenesis.

Cheffer, Arquimedes
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 19/06/2013 PT
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O receptor P2X4 (canal iônico controlado por adenosina-5'-trifosfato-ATP) está amplamente distribuído no sistema nervoso central e, após sua ativação, pode regular os níveis de cálcio intracelulares via permeação direta e por ativação de canais de cálcio voltagem-dependentes. Tem sido proposto que a atividade do receptor pode ser importante na plasticidade sináptica. Tendo em vista a importância do receptor P2X4, sobretudo na fisiologia do sistema nervoso central, é útil caracterizá-lo farmacologicamente e entender os mecanismos moleculares que regulam sua atividade. Examinamos o papel que resíduos específicos N- e C-terminais desempenham na atividade do receptor P2X4 humano, combinando técnicas de biologia molecular, bioquímica e patch-clamp em células de rim de embrião humano (células HEK-293T). Células HEK-293T expressando o receptor P2X4 wild-type apresentaram correntes iônicas, cujas amplitudes dependeram da concentração de ATP, fornecendo um valor de EC50 de 1,37 ± 0,21 µM. Os receptores mutantes E14A e D16A exibiram respostas ao ATP equiparáveis àquelas do receptor selvagem, ao passo que os mutantes Y15A e T17A não foram funcionais, apesar de serem expressos na membrana plasmática das células. A inibição de tirosina fosfatases por pervanadato diminuiu fortemente correntes induzidas por ATP. Subsequente análise de citometria de fluxo na presença de um anticorpo contra resíduos de fosfotirosina indicaram que...

Respostas de frangos de corte a aumentos graduais na relação entre treonina e lisina; Broiler responses to graded increases in the threonine to lysine ratio

Berres, Josemar; Vieira, Sérgio Luiz; Coneglian, Jorge Luis Bernardon; Olmos, Alexandra Reali; Freitas, Dimitri Moreira de; Bortolini, Tatsi Carolina Kowal; Silva, Guilherme Xavier da
Fonte: Universidade Federal do Rio Grande do Sul Publicador: Universidade Federal do Rio Grande do Sul
Tipo: Artigo de Revista Científica Formato: application/pdf
POR
Relevância na Pesquisa
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Um experimento foi conduzido com o objetivo de avaliar o efeito de relações crescentes entre treonina (Thr) e lisina (Lys) digestível em dietas de frangos de corte nas repostas produtivas dos 15 aos 37 dias de idade. Os aumentos dos níveis de treonina das dietas foram obtidos a partir de inclusões crescentes de farelo de soja (FS) ou L-treonina (L-Thr). Foram alojados 1.200 frangos de corte machos Ross x Ross 308 em arranjo fatorial com três relações entre Thr e Lys (63,5, 66,0 e 68,5%) e as duas fontes de Thr supracitadas. Cada um dos seis tratamentos foi constituído por oito repetições de 25 aves. As dietas foram formuladas para garantir o nível mínimo de exigência para os demais nutrientes e energia. Não houve efeito do nível de treonina sobre respostas de desempenho zootécnico, consumo de água, matéria seca da cama, lesões de pododermatite e rendimento de carcaça e cortes. Também não foi observado efeito da fonte de Thr sobre peso corporal, consumo de dieta, matéria seca da cama, lesões de pododermatite, rendimentos de carcaça, filé de peito, coxas e sobrecoxas. Entretanto, a conversão alimentar foi melhor (P=0,009) e o consumo de água maior (P=0,011) quando o aumento em Thr foi originado do FS, enquanto o rendimento de peito foi superior (P=0...

Protective effect of mannan oligosaccharides against early colonization by Salmonella Enteritidis in chicks is improved by higher dietary threonine levels

Santos, E. G.; Costa, F. G P; Silva, J. H V; Martins, T. D D; Figueiredo-Lima, D. F.; Macari, Marcos; Oliveira, C. J B; Givisiez, P. E N
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 1158-1165
ENG
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Aims: To evaluate mannan oligosaccharide (MOS) and threonine effects on performance, small intestine morphology and Salmonella spp. counts in Salmonella Enteritidis-challenged birds. Methods and Results: One-day-old chicks (1d) were distributed into five treatments: nonchallenged animals fed basal diet (RB-0), animals fed basal diet and infected with Salmonella Enteritidis (RB-I), animals fed high level of threonine and infected (HT-I), birds fed basal diet with MOS and infected (MOS-I), birds fed high level of threonine and MOS and infected (HT+MOS-I). Birds were inoculated at 2d with Salmonella Enteritidis, except RB-0 birds. Chicks fed higher dietary threonine and MOS showed performance similar to RB-0 and intestinal morphology recovery at 8 dpi. Salmonella counts and the number of Salmonella-positive animals were lower in HT+MOS-I compared with other challenged groups. Conclusion: Mannan oligosaccharides and threonine act synergistically, resulting in improved intestinal environment and recovery after Salmonella inoculation. Significance and Impact of the Study: Nutritional approaches may be useful to prevent Salmonella infection in the first week and putative carcass contamination at slaughter. This is the first report on the possible synergistic effect of mannan oligosaccharides and threonine...

Effects of different levels of dietary crude protein and threonine on performance, humoral immune responses and intestinal morphology of broiler chicks

Abbasi,MA; Mahdavi,AH; Samie,AH; Jahanian,R
Fonte: Fundação APINCO de Ciência e Tecnologia Avícolas Publicador: Fundação APINCO de Ciência e Tecnologia Avícolas
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/03/2014 EN
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The present study aimed at investigating the effects of different dietary crude protein (CP) and threonine (Thr) levels on the performance, immune responses and jejunal morphology of broiler chicks. A total of 432 broiler chicks were randomly assigned to a 3×3 factorial arrangement of treatments including three different CP dietary levels (90, 95, and 100% of Ross 308 recommendations) and Thr (100, 110, and 120% of Ross specifications) dietary levels. Performance parameters were recorded for the starter (1-12 days), grower (13-24 days) and finisher (25-42 days) periods. Birds were subjected to different antigen inoculations to evaluate antibody responses. At day 42 of age, two randomly-selected birds per replicate were slaughtered to measure carcass traits. Although Thr dietary supplementation had no marked effect on Newcastle antibody titers, particularly the supplementation of Thr up to 110% of Ross specifications improved (p<0.05) antibody titers against sheep red blood cells during both primary and secondary responses. Reduction of dietary CP level resulted in significant decrease in villus height (p<0.05) and crypt depth (p<0.01) in jejunal epithelial cells, but the supplementation of low-CP diets with Thr up to 110 and 120% of the recommended values allowed overcoming these changes. Except for the starter period...

Isolation of enzymes involved in threonine biosynthesis from sorghum seeds

Ferreira,Renato Rodrigues; Vendemiatti,Ariane; Meinhardt,Lyndel Wayne; Lea,Peter John; Azevedo,Ricardo Antunes
Fonte: Brazilian Journal of Plant Physiology Publicador: Brazilian Journal of Plant Physiology
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/08/2004 EN
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Cereal seeds are poor in essential amino acids, particularly lysine, tryptophan and threonine. The amino acids lysine and threonine are synthesized in the aspartate pathway. Although most of the enzymes of the aspartate pathway have been isolated and characterized in higher plant species, the metabolism of lysine and threonine is totally unknown in sorghum. We have isolated two enzymes, aspartate kinase (AK) and homoserine dehydrogenase (HSDH) from sorghum. Optimum assay conditions were established for the determination of AK and HSDH activities. The highest level of activity was observed in immature seeds. AK was shown to be inhibited by threonine and lysine indicating the existence of at least two isoenzymes, one sensitive to threonine inhibition and the other sensitive to lysine inhibition with the latter being predominant in sorghum seeds. HSDH was shown to be inhibited by threonine indicating the existence of a threonine-sensitive HSDH, however, most of the activity was not inhibited by threonine, suggesting the existence of a second predominant isoenzyme of HSDH resistant to threonine inhibition.

Threonine-lysine ratio on the requirements of digestible lysine in diets for broilers: lisina sobre a exigência de lisina digestível em dietas para frangos de corte

Ospina-Rojas,Iván Camilo; Murakami,Alice Eiko; Eyng,Cinthia; Picoli,Karla Paola; Scapinello,Claudio; Duarte,Cristiane Regina do Amaral
Fonte: Editora da Universidade Estadual de Maringá - EDUEM Publicador: Editora da Universidade Estadual de Maringá - EDUEM
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/2014 EN
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Two experiments were performed to determine the influence of threonine-lysine (Thr:Lys) ratio on requirements of digestible lysine (Lys) in low crude protein diets for broilers in the growth phase. In the first experiment, a total of 480 Cobb 500 male broilers were distributed in a completely randomized experimental design with four dietary Thr:Lys ratio (57.0; 60.5; 64.0 and 67.5%) and with five replicates of 24 birds each. No significant differences were reported in weight gain, feed intake, poultry manure humidity, carcass and meat yields. However, the feed conversion was increased linearly as dietary Thr:Lys ratio was increased. In the second experiment, a total of 400 Cobb 500 male broilers were distributed in a completely randomized experimental design with four digestible Lys levels (1.005, 1.045, 1.085 and 1.125%), and with four replicates of 25 birds each. No significant differences were reported in performance, poultry litter humidity and carcass and meat yields. Lys levels of 1.005% and Thr:Lys at 57% were sufficient to maximize the performance and carcass yield of broilers during the growth phase when fed on low crude protein diets.

Threonine degradation by Serratia marcescens.

Komatsubara, S; Murata, K; Kisumi, M; Chibata, I
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1978 EN
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The wild strain of Serratia marcescens rapidly degraded threonine and formed aminoacetone in a medium containing glucose and urea. Extracts of this strain showed high threonine dehydrogenase and "biosynthetic" threonine deaminase activities, but no threonine aldolase activity. Threonine dehydrogenase-deficient strain Mu-910 was selected among mutants unable to grow on threonine as the carbon source. This strain did not form aminoacetone from threonine, but it slowly degraded threonine. Strain D-60, deficient in both threonine dehydrogenase and threonine deaminase, was derived from strain Mu-910 and barely degraded threonine. A glycine-requiring strain derived from the wild strain grew in minimal medium containing threonine as the glycine source, whereas a glycine-requiring strain derived from strain Mu-910 did not grow. This indicates that threonine dehydrogenase participates in glycine formation from threonine (via alpha-amino-beta-ketobutyrate) as well as in threonine degradation to aminoacetone.

In Vivo Regulation of Threonine and Isoleucine Biosynthesis in Lemna paucicostata Hegelm. 6746

Giovanelli, John; Mudd, S. Harvey; Datko, Anne H.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1988 EN
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Little, if any, regulation of threonine synthesis was observed in Lemna paucicostata Hegelm. 6746 supplemented with concentrations of threonine and/or isoleucine that allow for uptake of these amino acids in amounts sufficient for total plant requirements, and that increase tissue concentrations of soluble threonine manyfold. High tissue concentrations of soluble threonine generated endogenously in isoleucine-supplemented plants were no more effective in regulation than a similar concentration of threonine accumulated from the medium. These studies exclude also major regulation of threonine biosynthesis by bivalent repression by threonine plus isoleucine. Isoleucine biosynthesis was severely inhibited by supplementation with isoleucine, but not with threonine or methionine. The fivefold increase in soluble threonine in isoleucine-supplemented plants suggests that threonine dehydratase is a major locus for feedback regulation of isoleucine synthesis. It is concluded that regulation of threonine biosynthesis differs from that of the other amino acids of the aspartate family (isoleucine, methionine, and lysine), each of which strongly feedback regulates its own synthesis. Methionine supplementation had a negligible effect on the tissue concentration of soluble threonine...

Metabolic homoeostasis of L-threonine in the normally-fed rat. Importance of liver threonine dehydrogenase activity.

Bird, M I; Nunn, P B
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/09/1983 EN
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Threonine dehydratase, threonine aldolase and threonine dehydrogenase activities were assayed in livers of rats that had been normally-fed, starved for 72 h, fed a high-protein diet or normally-fed and injected with glucagon or cortisone. A modified continuous spectrophotometric assay for threonine aldolase overcame interference resulting from threonine dehydratase activity and revealed that threonine aldolase activity was very low in rat liver, irrespective of the metabolic state of the animal. The concentration of free threonine was determined in livers of animals subjected to the same treatments as described above. Using Michaelis-Menten kinetics to estimate enzyme activities in vivo at intracellular threonine concentrations it was calculated that in the normally-fed state, 87% of the threonine degraded was catabolized by threonine dehydrogenase. In other metabolic states (except in glucagon-treated animals) threonine dehydratase was the major enzyme catalysing threonine catabolism. It was concluded that threonine dehydrogenase activity plays a hitherto unrecognized role in the metabolic homoeostasis of threonine in the normally-fed rat and that this enzyme activity, in association with 2-amino-3-oxobutyrate CoA-ligase, accounts for the known rate of glycine formation from threonine in the rat.

l-Threonine Regulates G1/S Phase Transition of Mouse Embryonic Stem Cells via PI3K/Akt, MAPKs, and mTORC Pathways*

Ryu, Jung Min; Han, Ho Jae
Fonte: American Society for Biochemistry and Molecular Biology Publicador: American Society for Biochemistry and Molecular Biology
Tipo: Artigo de Revista Científica
EN
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Although amino acids can function as signaling molecules in the regulation of many cellular processes, mechanisms surrounding l-threonine involvement in embryonic stem cell (ESC) functions have not been explored. Thus, we investigated the effect of l-threonine on regulation of mouse (m)ESC self-renewal and related signaling pathways. In l-threonine- depleted mESC culture media mRNA of self-renewal marker genes, [3H]thymidine incorporation, expression of c-Myc, Oct4, and cyclins protein was attenuated. In addition, resupplying l-threonine (500 μm) after depletion restores/maintains the mESC proliferation. Disruption of the lipid raft/caveolae microdomain through treatment with methyl-β-cyclodextrin or transfection with caveolin-1 specific small interfering RNA blocked l-threonine-induced proliferation of mESCs. Addition of l-threonine induced phosphorylation of Akt, ERK, p38, JNK/SAPK, and mTOR in a time-dependent manner. This activity was blocked by LY 294002 (PI3K inhibitor), wortmannin (PI3K inhibitor), or an Akt inhibitor. l-threonine-induced activation of mTOR, p70S6K, and 4E-BP1 as well as cyclins and Oct4 were blocked by PD 98059 (ERK inhibitor), SB 203580 (p38 inhibitor) or SP 600125 (JNK inhibitor). Furthermore, l-threonine induced phosphorylation of raptor and rictor binding to mTOR was completely inhibited by 24 h treatment with rapamycin (mTOR inhibitor); however...

Evaluation of Optimum Dietary Threonine Requirement by Plasma Free Threonine and Ammonia Concentrations in Surgically Modified Rainbow Trout, Oncorhynchus mykiss

Yun, Hyeonho; Park, Gunjun; Ok, Imho; Katya, Kumar; Heung, Silas; Bai, Sungchul C.
Fonte: Asian-Australasian Association of Animal Production Societies (AAAP) and Korean Society of Animal Science and Technology (KSAST) Publicador: Asian-Australasian Association of Animal Production Societies (AAAP) and Korean Society of Animal Science and Technology (KSAST)
Tipo: Artigo de Revista Científica
Publicado em /04/2015 EN
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This study was carried out to evaluate the dietary threonine requirement by measuring the plasma free threonine and ammonia concentrations in rainbow trout, Oncorhynchus mykiss after dorsal aorta cannulation. A total of 70 fish (average initial weight 506±8.2 g) were randomly distributed into each of the 14 net cages (5 fish/cage). After 48 hours (h) of feed deprivation, each group was intubated at 1% body weight with one of the seven L-amino acid based diets containing graded levels of threonine (0.42%, 0.72%, 0.92%, 1.12%, 1.32%, 1.52%, or 1.82% of diet, dry matter basis). Blood samples were taken at 0, 5, and 24 h after intubation. Post-prandial plasma free threonine concentrations (PPthr) of fish 5 h after intubation with diets containing 1.32% or more threonine were significantly higher than those of fish intubated with diets containing 1.12% or less threonine (p<0.05). Post-absorptive free threonine concentrations (PAthr) after 24 h of intubation of the fish with diets containing 0.92% or more threonine were significantly higher than those of fish intubated with diets containing 0.72% or less threonine. Post-prandial plasma ammonia concentrations (PPA, 5 h after intubation) were not significantly different among fish intubated with diets containing 1.12% or less threonine...

Níveis de treonina digestível em dietas para fêmeas suínas lactantes de médio potencial genético

Kiefer, Charles; Ferreira, Aloízio Soares; Donzele, Juarez Lopes; Oliveira, Rita Flávia Miranda de; Silva, Francisco Carlos de Oliveira; Carrijo, Alfredo Sampaio
Fonte: Revista Brasileira de Zootecnia Publicador: Revista Brasileira de Zootecnia
Tipo: Artigo de Revista Científica
POR
Relevância na Pesquisa
262.48922%
Foram utilizadas 76 fêmeas suínas lactantes de médio potencial genético com peso inicial de 207,0 ± 32,0 kg e ordem de parto de 3,53 ± 2,11, para avaliar níveis de treonina digestível na fase de lactação. Os animais foram distribuídos em delineamento experimental de blocos ao acaso, composto por quatro tratamentos (0,589; 0,627; 0,665 e 0,703% de treonina digestível) e 19 repetições, em que cada unidade experimental foi constituída por uma fêm ea. Não houve efeito dos níveis de treonina digestível sobre o peso das fêmeas ao desmame, a espessura de toucinho (ET) e a composição de proteína corporal à desmama. A perda de peso das fêmeas durante a lactação reduziu de forma linear com o aumento do nível de treonina digestível. Os níveis de treonina digestível não influenciaram a variação da ET durante a lactação, mas afetaram a mobilização de proteína corporal, que reduziu linearmente com o aumento do nível de treonina digestível. Não houve efeito dos níveis de treonina digestível sobre os consumos de ração, de lisina e de energia digestível, entretanto, verificou-se aumento linear do consumo de treonina digestível, em razão do aumento de seu nível na dieta. Os níveis de treonina digestível não influenciaram a eficiência energética das fêmeas...

Níveis de treonina digestível em dietas para fêmeas suínas de alto potencial genético em lactação sob condições de alta temperatura ambiente

Kiefer, Charles; Ferreira, Aloízio Soares; Oliveira, Rita Flávia Miranda de; Donzele, Juarez Lopes; Carrijo, Alfredo Sampaio; Silva, Francisco Carlos de Oliveira
Fonte: Revista Brasileira de Zootecnia Publicador: Revista Brasileira de Zootecnia
Tipo: Artigo de Revista Científica
POR
Relevância na Pesquisa
262.92928%
Foram utilizadas 52 fêmeas suínas em lactação distribuídas em delineamento experimental de blocos ao acaso, composto de quatro níveis de treonina digestível (0,64; 0,67; 0,70 e 0,73%) na dieta e 13 repetições, em que cada unidade experimental foi constituída por uma fêmea. A temperatura do ar no interior das salas foi de 29,7 ± 2,5oC. Não houve efeito dos níveis de treonina digestível na dieta sobre o peso das fêmeas ao desmame. As perdas total e percentual de peso das fêmeas durante a lactação reduziram de forma linear com o aumento dos níveis de treonina digestível na dieta. Os níveis de treonina digestível influenciaram a espessura de toucinho (ET) ao desmame e afetaram as variações total e percentual de espessura de toucinho. As composições de gordura e proteína corporal à desmama não foram influenciadas pelos níveis de treonina digestível na dieta. Verificou-se redução linear das mobilizações total e percentual de gordura corporal conforme aumentaram os níveis de treonina digestível na dieta. A mobilização de proteína corporal, a produção de leite e o intervalo desmama-estro não foram influenciados pelos níveis de treonina digestível da dieta. Os níveis de treonina digestível não afetaram os consumos de ração...

Disruption of the Serine/Threonine kinase 9 gene causes severe X-linked infantile spasms and mental retardation

Kalscheuer, V.; Tao, J.; Donnelly, A.; Hollway, G.; Schwinger, E.; Kubart, S.; Menzel, C.; Hoeltzenbein, M.; Tommerup, N.; Eyre, H.; Harbord, M.; Haan, E.; Sutherland, G.; Ropers, H.H.; Gecz, J.
Fonte: Univ Chicago Press Publicador: Univ Chicago Press
Tipo: Artigo de Revista Científica
Publicado em //2003 EN
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X-linked West syndrome, also called "X-linked infantile spasms" (ISSX), is characterized by early-onset generalized seizures, hypsarrhythmia, and mental retardation. Recently, we have shown that the majority of the X-linked families with infantile spasms carry mutations in the aristaless-related homeobox gene (ARX), which maps to the Xp21.3-p22.1 interval, and that the clinical picture in these patients can vary from mild mental retardation to severe ISSX with additional neurological abnormalities. Here, we report a study of two severely affected female patients with apparently de novo balanced X;autosome translocations, both disrupting the serine-threonine kinase 9 (STK9) gene, which maps distal to ARX in the Xp22.3 region. We show that STK9 is subject to X-inactivation in normal female somatic cells and is functionally absent in the two patients, because of preferential inactivation of the normal X. Disruption of the same gene in two unrelated patients who have identical phenotypes (consisting of early-onset severe infantile spasms, profound global developmental arrest, hypsarrhythmia, and severe mental retardation) strongly suggests that lack of functional STK9 protein causes severe ISSX and that STK9 is a second X-chromosomal locus for this disorder.

Conversion of [U-14C]threonine into 14C-labelled amino acids in the brain of thiamin-deficient rats.

Gaitonde, M K
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1975 EN
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In confirmation of the findings of Gaitonde et al. (1974), a decrease in the brain concentration of threonine and serine, and an increase in glycine, were observed in rats maintained on a thiamin-deficient diet. Similar changes were found in the blood, and the concentration of several other amino acids in the blood decreased significantly. There was a correlation between the concentrations of threonine, serine, aspartate and asparagine in the brain and blood. In experiments in which [U-14C]threonine was injected into rats most of the radioactivity in the brain and blood of control rats was, as expected, in threonine in the acid soluble metabolites. In contrast, a considerable proportion of radioactivity was also found in other amino acids, namely glutamate, glutamine, aspartate, gamma-aminobutyrate and alanine, in the brain of thiamin-deficient rats. [U-14C]Threonine was also converted into 14C-labelled lactate and glucose, but the extent of this conversion was severalfold higher in thiamin-deficient than in control rats. This finding gave evidence of the stimulation in thiamin-deficient rats of the catabolism of [U-14C]threonine to [14C]lactate by the aminoacetone pathway catalysed by threonine dehydrogenase, and into succinate via propionate by the alpha-oxobutyrate pathway catalysed by threonine dehydratase (deaminase). The measurement of specific radioactivities of glutamate...

Utilization of l-threonine by a species of Arthrobacter. A novel catabolic role for `aminoacetone synthase'

McGilvray, D.; Morris, J. G.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /05/1969 EN
Relevância na Pesquisa
264.65467%
1. A species of Arthrobacter (designated Arthrobacter 9759) was isolated from soil by its ability to grow aerobically on l-threonine as sole source of carbon atoms, nitrogen atoms and energy; the organism also grew well on other sources of carbon atoms including glycine, but no growth was obtainable on aminoacetone or dl-1-aminopropan-2-ol. 2. During growth on threonine, 14C from l-[U-14C]threonine was rapidly incorporated into glycine and citrate, and thereafter into serine, alanine, aspartate and glutamate. 3. With extracts of threonine-grown cells supplied with l-[U-14C]threonine, evidence was obtained of the NAD and CoA-dependent catabolism of l-threonine to produce acetyl-CoA plus glycine. Short-term incorporation studies in which [2-14C]acetate and [2-14C]glycine were supplied (a) to cultures growing on threonine, and (b) to extracts of threonine-grown cells, showed that the acetyl-CoA was metabolized via the tricarboxylic acid cycle and glyoxylate cycle whereas the glycine was converted into pyruvate via the folate-dependent `serine pathway'. 4. The threonine-grown organism contained `biosynthetic' threonine dehydratase and a potent NAD-linked l-threonine dehydrogenase but possessed no l-threonine aldolase activity. 5. Evidence was obtained that the acetyl-CoA and glycine produced from l-threonine had their immediate origin in the α-amino-β-oxobutyrate formed by the threonine dehydrogenase; the CoA-dependent cleavage of this compound was catalysed by an α-amino-β-oxobutyrate CoA-ligase...

Bacterial catabolism of threonine. Threonine degradation initiated by l-threonine hydrolyase (deaminating) in a species of Corynebacterium

Bell, Stephen C.; Turner, John M.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/06/1977 EN
Relevância na Pesquisa
263.31145%
1. Three bacterial isolates capable of growth on l-threonine medium only when supplemented with branched-chain amino acids, and possessing high l-threonine dehydratase activity, were examined to elucidate the catabolic route for the amino acid. 2. Growth, manometric, radiotracer and enzymic experiments indicated that l-threonine was catabolized by initial deamination to 2-oxobutyrate and thence to propionate. No evidence was obtained for the involvement of l-threonine 3-dehydrogenase or l-threonine aldolase in threonine catabolism. 3. l-Threonine dehydratase of Corynebacterium sp. F5 (N.C.I.B. 11102) was partially purified and its kinetic properties were examined. The enzyme exhibited a sigmoid kinetic response to substrate concentration. The concentration of substrate giving half the maximum velocity, [S0.5], was 40mm and the Hill coefficient (h) was 2.0. l-Isoleucine inhibited enzyme activity markedly, causing 50% inhibition at 60μm, but did not affect the Hill constant. At the fixed l-threonine concentration of 10mm, the effect of l-valine was biphasic, progressive activation occurring at concentrations up to 2mm-l-valine, but was abolished by higher concentrations. Substrate-saturation plots for the l-valine-activated enzyme exhibited normal Michaelis–Menten kinetics with a Hill coefficient (h) of 1.0. The kinetic properties of the enzyme were thus similar to those of the `biosynthetic' isoenzyme from Rhodopseudomonas spheroides rather than those of the enteric bacteria. 4. The synthesis of l-threonine dehydratase was constitutive and was not subject to multivalent repression by l-isoleucine or other branched-chain amino acids either singly or in combination. 5. The catabolism of l-threonine...

Expression of the Serine/Threonine Kinase hSGK1 in Chronic Viral Hepatitis

Fillon, S; Klingel, Karen; Warntges, Simone; Sauter, Martina; Gabrysch, S; Pestel, Sabine; Tanneur, Valerie; Waldegger, S; Zipfel, Annette; Viebahn, R; Haussinger, D; Broer, Stefan; Kandolf, Reinhart; Lang, Florian
Fonte: S Karger AG Publicador: S Karger AG
Tipo: Artigo de Revista Científica
Relevância na Pesquisa
349.09867%
The human serine/threonine kinase hSGK1 is expressed ubiquitously with highest transcript levels in pancreas and liver. This study has been performed to determine the hSGK1 distribution in normal liver and its putative role in fibrosing liver disease. HSGK1-localization was determined by in situ hybridization, regulation of hSGK1-transcription by Northern blotting, fibronectin synthesis and hSGK1 phosphorylation by Western blotting. In normal liver hSGK1 was mainly transcribed by Kupffer cells. In liver tissue from patients with chronic viral hepatitis, hSGK1 transcript levels were excessively high in numerous activated Kupffer cells and inflammatory cells localized within fibrous septum formations. HSGK1 transcripts were also detected in activated hepatic stellate cells. Accordingly, Western blotting revealed that tissue from fibrotic liver expresses excessive hSGK1 protein as compared to normal liver. TGF-β1 (2 ng/ml) increases hSGK1 transcription in both human U937 macrophages and HepG2 hepatoma cells. H2O2 (0.3 mM) activated hSGK1 and increased fibronectin formation in HepG2 cells overexpressing hSGK1 but not in HepG2 cells expressing the inactive mutant hSGK1K127R. In conclusion hSGK1 is upregulated by TGF-β1 during hepatitis and may contribute to enhanced matrix formation during fibrosing liver disease.