RESUMO
Cyclodextran (CI) is a cyclic oligosaccharide in which d-glucose forms a ring structure by α-1,6 glycoside linkage and forms an inclusion complex with various guest molecules. In this study, we conducted quantum chemical calculations and molecular dynamics (MD) simulations to analyze the molecular interaction mechanism of CI with a guest molecule. Calculations of cyclodextrin (CD), in which d-glucose forms a ring structure by α-1,4 glycoside linkage, were also performed for comparison. Here, coenzyme Q10 (CoQ10), a promising molecule for industrial application with CI, was chosen as a guest molecule. Our MD simulation demonstrated that the molecular fluctuation was similarly large for both CI and CD when CoQ10 was absent. In the case that CoQ10 exists, the CD was found to form a rigid one-by-one inclusion structure, while CI does not. Additional simulations including multiple CI-8s indicated the possibility that an inclusion structure is maintained by the existence of other CI-8s.
Assuntos
Ciclodextrinas , Ciclodextrinas/química , Simulação de Dinâmica Molecular , Glicosídeos , GlucoseRESUMO
AIMS: Hypertension causes proteinuria and is an important factor in the progress of renal dysfunction. Increases in various proteins in urine are caused by malfunction of the glomerulus and the renal tubules. In the present study, the effects of hypertension on urinary excretion levels of various proteins were investigated to show the tubular cell malfunction in hypertensive patients. METHODS AND SUBJECTS: The subjects included 55 non-diabetic hypertensive patients without previous treatment and 42 normotensive individuals without microalbuminuria. Total urinary protein/creatinine ratio was measured, and urinary proteins were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). FINDINGS: Total urinary protein/creatinine ratio was higher in hypertensive patients than in normotensive individuals (122.0+/-11.0 vs. 60.6+/-3.1 mg/gCr; p<0.001). SDS-PAGE resolved 15 protein fractions from the urine of both groups. Thirteen fractions were more intensely stained in samples from the hypertensive than from the normotensive. Two fractions did not differ between the groups. Hypertension increased the urinary excretion of various proteins including proteins of less than 40 kDa, called tubular proteins, in addition to albumin. CONCLUSIONS: Hypertension differently influenced the excretion of each urinary protein fraction. Tubular malfunction should be considered in hypertensive patients in addition to glomerular malfunction.
Assuntos
Albuminúria , Hipertensão/urina , Proteinúria , Eletroforese em Gel de Poliacrilamida , Feminino , Humanos , Glomérulos Renais/fisiopatologia , Túbulos Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Proteínas/análiseRESUMO
Asparagine synthetase (ASNS), 3-phosphoglycerate dehydrogenase (PHGDH) and serine dehydratase (SDS) in rat liver are expressed in response to protein and amino acid intake. In the present study, we examined the expression of these enzymes in relation to amino acid imbalance caused by leucine. Rats were subjected to leucine administration in the diet or orally between meals. Consumption of more than 2% leucine in a 6% casein diet suppressed food intake and caused growth retardation in a dose-dependent manner, but this was not seen in a 12% or 40% casein diet. ASNS and PHGDH expression in the liver was significantly induced by the 6% casein diet and was suppressed by leucine in a dose-dependent manner, whereas the SDS expression was induced. These effects were leucine specific and not seen with ingestion of isoleucine or valine. However, leucine orally administered between meals did not change the food intake or growth of rats fed a 6% casein die, though it similarly affected the expression of ASNS, PHGDH and SDS in the liver. These results suggest that the growth retardation caused by leucine imbalance was mainly because of the suppression of food intake, and demonstrated that there are no causal relationships between ASNS, PHGDH and SDS expression and amino acid imbalance caused by leucine.
Assuntos
Aspartato-Amônia Ligase/metabolismo , Dieta , Ingestão de Alimentos/efeitos dos fármacos , L-Serina Desidratase/metabolismo , Leucina/efeitos adversos , Fígado/efeitos dos fármacos , Fosfoglicerato Desidrogenase/metabolismo , Aminoácidos/administração & dosagem , Aminoácidos/metabolismo , Animais , Peso Corporal , Caseínas/administração & dosagem , Regulação para Baixo , Ingestão de Energia/efeitos dos fármacos , Crescimento/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Isoleucina/farmacologia , Leucina/administração & dosagem , Fígado/metabolismo , Masculino , Ratos Sprague-Dawley , Ativação Transcricional , Regulação para Cima , Valina/farmacologiaRESUMO
The present study was conducted to identify reliable gene biomarkers for the adverse effects of excessive leucine (Leu) in Sprague-Dawley rats by DNA microarray. It has long been known that the adverse effects of excessive amino acid intake depend on dietary protein levels. Male rats were divided into 12 groups (n=6) and fed for 1 wk a diet containing low (6%), moderate (12%) or high (40%) protein. Different levels of Leu (0, 2, 4, and 8%) were added to the diets. Consumption of diets containing more than 4% Leu in 6% protein resulted in growth retardation and reduced liver weight, whereas the administration of the same dose of Leu with 12% or 40% protein did not affect them. By a process of systematic data extraction, 6 candidate gene markers were identified. The liver gene expression data obtained from another experiment with 0, 2, 3, 4, and 8% Leu in a low-protein diet was used to examine the validity of these biomarker candidates with receiver operating characteristic (ROC) curve analysis. All of AUC values of the biomarker candidates were more than 0.700, suggesting the effectiveness of the marker candidates as the indices of Leu excess. The cut-off value for the ROC curve of the gene-marker panel, which was obtained by multiple regression analysis of gene markers, indicated that Leu levels higher than 3% have adverse effects. In conclusion, the gene-marker panel suggested that for male rats dietary Leu supplementation of 2% is the NOAEL dose in low-protein (6%) diets.