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La actividad de la aciltransferasa de la hidrolasa de sales biliares expande la diversidad de ácidos biliares
Douglas V Guzior1,2, Maxwell Okros1, Madison Shivel1,3
1Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA.
Nature
|February 7, 2024
Resumen
Los investigadores descubrieron que las enzimas de la hidrolasa de sales biliares (BSH / T) en las bacterias intestinales pueden unir aminoácidos a los ácidos biliares (BA), creando ácidos biliares microbialmente conjugados (MCBA). Estos MCBA tienen propiedades antimicrobianas y son abundantes en el intestino humano.
Área de la Ciencia:
- Microbiología
- La bioquímica
- Investigación del microbioma intestinal
Sus antecedentes:
- Los ácidos biliares (BA) son cruciales para la absorción de grasa y la modulación del microbioma intestinal debido a sus efectos antimicrobianos.
- Las bacterias intestinales metabolizan BAs, pero las enzimas y los mecanismos específicos para la conjugación de aminoácidos eran en gran medida desconocidos.
Objetivo del estudio:
- Identificar la enzima responsable de la conjugación de aminoácidos de BA por la microbiota intestinal.
- Caracterizar las propiedades y la importancia biológica de los ácidos biliares microbialmente conjugados (MCBA) resultantes.
Principales métodos:
- Pruebas enzimáticas con Clostridium perfringens BSH/T con varios aminoácidos y BA.
- Análisis de las relaciones estructura-función BSH/T a través del mapeo de la estructura terciaria y la mutagénesis.
- Pruebas de actividad antimicrobiana de los MCBA.
- Estudios in vivo en ratones para el seguimiento de la circulación enterohepática de MCBA.
- Cuantificación de MCBA en muestras fecales humanas y correlación con los resultados de la cirugía bariátrica.
Principales resultados:
- La enzima hidrolasa / transferasa de sales biliares (BSH / T) media la conjugación de aminoácidos con BA, produciendo diversos MCBA.
- BSH/T exhibe una amplia selectividad de aminoácidos, con una actividad optimizada a pH 5,3.
- Los MCBA muestran propiedades antimicrobianas, con una actividad correlacionada con la hidrofobidad de los aminoácidos.
- Los MCBA están presentes en concentraciones significativas en el intestino humano y se ven afectados por la cirugía bariátrica.
Conclusiones:
- La actividad de la aciltransferasa de BSH/T expande significativamente la química de los ácidos biliares.
- Los MCBA son un componente sustancial y previamente subestimado de la reserva de ácidos biliares con impactos potenciales en el microbioma y la salud humana.
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