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Inhibición por óxido nítrico de las enzimas de radicales glicílicos y sus activasas
Juan Carlos Cáceres1, Nathan G Michellys2, Brandon L Greene1,2
1Interdisciplinary Program in Quantitative Biosciences, University of California Santa Barbara, Santa Barbara, California 93106, United States.
Journal of the American Chemical Society
|March 25, 2025
Resumen
El óxido nítrico (NO) inhibe las enzimas clave en el metabolismo anaeróbico, como la piruvato formato liasa (PFL), interrumpiendo el crecimiento bacteriano. Esta inhibición mediada por NO de las enzimas de los radicales glicílicos puede desempeñar un papel en la inmunidad intestinal.
Área de la Ciencia:
- Microbiología
- La bioquímica
- Inmunología
Sus antecedentes:
- Las células inmunes innatas generan óxido nítrico (NO) para combatir los patógenos.
- Se conocen los efectos antimicrobianos del NO contra las enzimas del metabolismo aeróbico.
- Sus objetivos en el metabolismo anaeróbico siguen siendo menos conocidos.
Objetivo del estudio:
- Investigar los objetivos moleculares del NO en el metabolismo anaeróbico.
- Para determinar el efecto del NO en la enzima piruvato formato liasa (PFL) del radical glicílico de Escherichia coli.
Principales métodos:
- Espectroscopia por resonancia paramagnética de electrones (EPR).
- Mutagénesis dirigida al sitio.
- EPR de células enteras y análisis de flujo metabólico.
- PFL investigado y su enzima activadora (PFL-AE).
Principales resultados:
- El NO inhibe irreversiblemente la PFL destruyendo su radical glicílico.
- El NO inactiva el PFL-AE, convirtiendo los grupos de hierro y azufre en complejos de hierro dinitrosil.
- Los niveles fisiológicamente relevantes de NO inhiben la PFL y la PFL-AE en *E. coli*, reduciendo el crecimiento y cambiando el metabolismo.
- Se observó una inhibición análoga para la ribonucleotida reductasa (RNR) de clase III y su enzima activadora (RNR-AE).
Conclusiones:
- NO inhibe ampliamente la química de las enzimas de los radicales glicílicos, incluidas las vías PFL y RNR.
- Esta inhibición contribuye a los efectos bacteriostáticos del NO.
- El NO puede funcionar inmunológicamente apuntando a las enzimas metabólicas anaerobias en el intestino.
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