RESUMEN
Advanced glycation end products (AGEs), which are the final products of glycation, have a major role in diabetic complication and neurodegenerative disorders. The 3-ß-hydroxybutyrate (3BHB), a ketone body which is produced by the liver, can be detected in increased concentrations in individuals post fasting and prolonged exercises and in diabetic (type I) patients. In this study, the inhibitory effect of 3BHB on AGEs formation by glucose from the human serum albumin (HSA) was studied at physiological conditions after 35 days of incubation, using physical techniques such as circular dichroism and fluorescence spectroscopy, as well as differential scanning calorimetry (DSC). The fluorescence intensity measurements of glycated HSA by glucose (GHSA) in the presence of 3BHB indicate a decrease in AGEs formation. The DSC deconvolution profile results also confirm the protective role of 3BHB on incubated with glucose by preventing the enthalpy reduction of the HSA tail segment, compared with the deconvolution profile seen for incubated with glucose alone. The concentration of 3BHB used in this study is in accordance with the concentration detected in the body of individuals post fasting and prolonged exercises.
Asunto(s)
Complicaciones de la Diabetes/metabolismo , Glucosa/metabolismo , Productos Finales de Glicación Avanzada/metabolismo , Albúmina Sérica/efectos de los fármacos , Ácido 3-Hidroxibutírico/administración & dosificación , Rastreo Diferencial de Calorimetría , Dicroismo Circular , Complicaciones de la Diabetes/patología , Ejercicio Físico/fisiología , Productos Finales de Glicación Avanzada/antagonistas & inhibidores , Productos Finales de Glicación Avanzada/química , Glicosilación/efectos de los fármacos , Humanos , Albúmina Sérica/metabolismo , Espectrometría de Fluorescencia , TermodinámicaRESUMEN
The molten globule (MG) state is an intermediate which is considered as the third thermodynamic state of protein molecules. In this work the effect of incubating human serum albumin (HSA) at physiological condition in the presence of 3-ß-hydroxybutyrate for 7, 14, 21 and 35 days were studied by different techniques such as UV/vis, fluorescence and circular dichroism (CD) spectroscopy, differential scanning calorimetry (DSC) and dynamic light scattering (DLS). In this paper, we introduce the MG state for HSA upon 21 days incubation with 3-ß-hydroxybutyrate as a ketone body at physiological condition. The results from the HSA sample incubated for 21 days shows a similar secondary structure by CD, more surface hydrophobicity and a little change on tertiary structure by fluorescence, and a larger size by DLS as compared to the native sample or other incubated samples. These results were also confirmed by calculated parameters and DSC deconvoluted thermograms.