RESUMO
Three compounds were isolated from Maytenus acanthophylla Reissek (Celastraceae): the pentacyclic triterpenes lup-20(29)-en-3ß-ol (lupeol, 1) and 3ß-lup-20(29)-en-3-yl acetate (2) and the carbohydrate 1,2,3,4,5,6-hexa-O-acetyldulcitol (3); lupeol was also isolated from Xylosma flexuosa. The compounds' structures were elucidated by spectroscopic and spectrometric analysis. Compound 1 acts as an energy transfer inhibitor, interacting with isolated CF1 bound to thylakoid membrane, and dulcitol hexaacetate 3 behaves as a Hill reaction inhibitor and as an uncoupler, as determined by polarography. Chlorophyll a (Chl a) fluorescence induction kinetics from the minimum yield F0 to the maximum yield F(M )provides information of the filling up from electrons coming from water to plastoquinone pool with reducing equivalents. In this paper we have examined the effects of compounds 1 and 3 on spinach leaf discs. Compound 1 induces the appearance of a K-band, which indicates that it inhibits the water splitting enzyme. In vivo assays measuring the fluorescence of chl a in P. ixocarpa leaves sprayed with compound 1, showed the appearance of the K-band and the PSII reaction centers was transformed to "heat sinks" or silent reaction centers unable to reduce Q(A). However, 3 also induced the appearance of a K band and a new band I appears in P. ixocarpa plants, therefore it inhibits at the water splitting enzyme complex and at the PQH2 site on b6f complex. Compounds 1 and 3 did not affect chlorophyll a fluorescence of L. perenne plants.
Assuntos
Galactitol/farmacologia , Luz , Fotossíntese/efeitos dos fármacos , Fotossíntese/efeitos da radiação , Triterpenos/farmacologia , ATPase de Ca(2+) e Mg(2+)/metabolismo , Clorofila/metabolismo , Clorofila A , Transporte de Elétrons/efeitos dos fármacos , Transporte de Elétrons/efeitos da radiação , Fluorescência , Galactitol/química , Cinética , Maytenus/química , Paraquat/metabolismo , Triterpenos Pentacíclicos/química , Triterpenos Pentacíclicos/farmacologia , Fosforilação/efeitos dos fármacos , Fosforilação/efeitos da radiação , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/efeitos da radiação , Spinacia oleracea/efeitos dos fármacos , Spinacia oleracea/metabolismo , Spinacia oleracea/efeitos da radiação , Tilacoides/efeitos dos fármacos , Tilacoides/enzimologia , Tilacoides/efeitos da radiação , Triterpenos/químicaRESUMO
OBJECTIVES: To determine the long-term outcome of dietary intervention in siblings from 14 Irish families with classical galactosemia (McKusick 230400), an autosomal recessive disorder of carbohydrate metabolism and galactose-1-phosphate uridyltransferase (GALT) deficiency. STUDY DESIGN: Outcomes in siblings on dietary galactose restriction were studied to evaluate whether birth order (ie, time of commencement of diet) and compliance with lactose-restricted diet (galactose intake > or < 20 mg /day), assessed by dietary recall and biochemical monitoring of galactose-1-phosphate [Gal-1-P] and galactitol values, affected outcomes. The outcome variables assessed were IQ, speech, and language assessment scores, neurologic examination results, and magnetic resonance imaging (MRI) of the brain. RESULTS: There was a high incidence of complications in the overall group, particularly speech and language delay (77%) and low IQ (71%). There was no significant difference in outcome between earlier-treated and later-treated siblings or any correlation with mean Gal-1-P or galactitol values. In most cases, cerebral white matter disease was evident on MRI scanning, with evidence of progressive cerebellar degeneration seen in 2 highly compliant families. CONCLUSION: The subjects with a higher galactose intake did not exhibit an increased incidence of complications; conversely, those who were very compliant with dietary restrictions did not have more favorable outcomes.
Assuntos
Encéfalo/patologia , Galactosemias/complicações , Galactosemias/dietoterapia , Testes de Inteligência , Transtornos da Linguagem/etiologia , Irmãos , Adolescente , Adulto , Ordem de Nascimento , Criança , Pré-Escolar , Registros de Dieta , Feminino , Galactitol/urina , Galactose/administração & dosagem , Galactosemias/genética , Galactosefosfatos/sangue , Humanos , Lactente , Irlanda , Lactose/administração & dosagem , Espectroscopia de Ressonância Magnética , Masculino , Exame Neurológico , Cooperação do Paciente , Estudos Retrospectivos , Adulto JovemRESUMO
Different conformations of methyl 3,6-anhydro-4-O-methyl-alpha-d-galactoside (1) and 3,6-anhydro-4-O-methylgalactitol (2) were studied by molecular mechanics (using the program mm3) and by quantum mechanical (QM) methods at the B3LYP/6-31+G( * *) and MP2/6-311++G( * *) levels, with and without solvent emulation. In 2, where the five-membered ring is free to move, two main stable conformations of this ring were found, identified as North (N) and South (S). The latter appears to be more stable, by either calculation, though the energy difference is reduced when emulating solution behavior. In order to find out the possible influence of a glycosidic bond over its shape, and to explain the marked NMR chemical shift displacements observed by opening of the ring, the adiabatic maps of two disaccharides carrying an analog of beta-galactoside linked to O-4 of 1 and 2 were generated. It was shown that the characteristics of the 3,6-AnGal terminal influence the characteristics of the map, especially at lower dielectric constants. On the other hand, different glycosidic angles also promote distinct stable conformations of the five-membered ring, changing from N to S, or even variants. Comparison with experimental results leads to the idea of highly flexible disaccharides, with variable values for both the five-membered ring and the glycosidic angles.
Assuntos
Dissacarídeos/química , Galactose/química , Configuração de Carboidratos , Cristalografia por Raios X/métodos , Galactitol/química , Glicosídeos , Espectroscopia de Ressonância Magnética , Modelos Químicos , Conformação Molecular , Estrutura Molecular , Teoria Quântica , Reprodutibilidade dos Testes , SoftwareRESUMO
The synthesis of alpha-D-galactofuranosyl-(1-->2)-D-galactitol, which has been isolated by reductive beta-elimination from glycoproteins of Bacteroides cellulosolvens and Clostridium thermocellum, is described. The approach of selective glycosylation of an aldono-1,4-lactone by the trichloroacetimidate method was employed. The synthesis of alpha-D-Gal f-(1-->2)[beta-D-Gal f-(1-->3)]-D-Galol, that contains Gal f units in both anomeric configurations, is also reported. These are the first synthetic oligosaccharides with alpha-D-Gal f, previously found in natural products.
Assuntos
Bacteroides/química , Galactitol , Galactose , Glicoproteínas/química , Trissacarídeos/síntese química , Sequência de Carboidratos , Indicadores e Reagentes , Modelos Moleculares , Dados de Sequência Molecular , Trissacarídeos/químicaRESUMO
We describe how proton MR spectroscopy ((1)H-MR spectroscopy) was useful in elucidating the diagnosis of galactosemia in an undiagnosed 6-month-old infant. In vivo (1)H-MR spectroscopy of the brain showed a doublet at 3.7 parts per million, which was identified as galactitol (Gal-ol) by in vitro (1)H-MR spectroscopy of the urine. Galactosemia was subsequently confirmed by laboratory tests and treatment was initiated. A follow-up brain MR imaging and (1)H-MR spectroscopy study revealed resolution of white matter lesions and disappearance of Gal-ol peaks.
Assuntos
Química Encefálica , Galactitol/análise , Galactosemias/diagnóstico , Espectroscopia de Ressonância Magnética , Encéfalo/patologia , Feminino , Galactitol/urina , Galactosemias/dietoterapia , Humanos , Lactente , Imageamento por Ressonância MagnéticaRESUMO
Las alteraciones del metabolismo de la galactosa se producen por el defecto de las enzimas: galactoquinasa (GALK), galactosa-1-fosfato-uridil transferasa (GAL1-PUT) y uridin difosfato galactosa 4' epimerasa (UDPGAL); de ellas la más frecuente es la galactosemia clásica producida por la deficiencia de GAL1PUT. Producto de este defecto se acumula galactosa-1-fosfato, galactosa libre y galactitol en sangre y tejidos, los que producen alteraciones hepáticas, renales y cerebrales. Su herencia es autosómica recesiva y la incidencia estimada a nivel mundial fluctúa entre 1:60.000 a 1:33.000 recién nacidos. Los síntomas y signos más característicos son vómito, diarrea, ictericia, hepatomegalia, cataratas. Si la enfermedad no es tratada oportunamente ocasiona la muerte del niño. El tratamiento consiste en eliminar la lactosa y galactosa de la alimentación, lo que incluye alimentos tales como la leche de todo tipo y sus derivados, la galactosa y alimentos o medicamentos que contenga alguno de estos productos. Se entrega leche de soya y los requerimientos de macro y micro nutrientes se indican según las recomendaciones para edad y sexo. La dieta dura toda la vida ya que la galactosa se transforma en galactitol, existiendo riesgo de producir catarata y daño renal en cualquier momento de la vida. Un buen control se obtiene al mantener el nivel sanguíneo de galactosa-1-fosfato igual o menor a 3.0 mg/dL y urinario de galactitol bajo 0.8 mmol/mol de creatinina.
Assuntos
Humanos , Galactose/metabolismo , Galactosemias/dietoterapia , Galactosemias/enzimologia , Catarata/etiologia , Galactitol/efeitos adversos , Galactosemias/complicações , Galactosemias/diagnóstico , Lactose/efeitos adversos , Laticínios/efeitos adversosRESUMO
In a newborn infant with galactose-1-phosphate uridyltransferase deficiency and encephalopathy, brain magnetic resonance imaging revealed cytotoxic edema in white matter. Using in vivo proton magnetic resonance spectroscopy, we detected approximately 8 mmol galactitol per kilogram of brain tissue, an amount potentially relevant to the pathogenesis of brain edema.