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La riboneogénesis en las levaduras.

Michelle F Clasquin1, Eugene Melamud, Alexander Singer

  • 1Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton NJ 08544, USA.

Cell
|June 14, 2011
PubMed
Resumen
Este resumen es generado por máquina.

Las levaduras utilizan la riboneogénesis para crear ribosa-5-fosfato a partir de los intermediarios de la glucólisis. Esta nueva vía, identificada por la enzima sedoheptulosa-1,7-bisfosfatasa (SHB17), evita la producción de NADPH.

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Área de la Ciencia:

  • Las vías metabólicas.
  • La bioquímica es la bioquímica.
  • Metabolismo de la levadura metabolismo de la levadura.

Sus antecedentes:

  • El catabolismo de la glucosa en la levadura se produce a través de la glucólisis y la vía oxidativa de la pentosa fosfato (PPP).
  • El PPP oxidativo produce NADPH y ribosa-5-fosfato, cruciales para la síntesis de nucleótidos.
  • Las vías existentes no producen eficientemente ribosa-5-fosfato independientemente del NADPH.

Objetivo del estudio:

  • Identificar y caracterizar una nueva vía metabólica para la síntesis de ribosa-5-fosfato en la levadura.
  • Para aclarar los pasos enzimáticos y la regulación de esta nueva vía, denominada riboneogénesis.
  • Comprender las condiciones bajo las cuales se favorece la riboneogénesis sobre la producción de NADPH.

Principales métodos:

  • Análisis metabólico de las cepas de levadura knockout.
  • Análisis de actividad enzimática. ensayos de actividad enzimática.
  • Determinación de la estructura de cristal de la sedoheptulosa-1,7-bisfosfatasa (SHB17).

Principales resultados:

  • Descubrimiento de la riboneogénesis, una vía que convierte los intermediarios glicolíticos en ribosa-5-fosfato sin producción de NADPH.
  • Identificación de la sedoheptulosa-1,7-bisfosfatasa (SHB17) como la enzima clave en el paso comprometido.
  • Análisis estructural de SHB17 unido a su sustrato, sedoheptulosa-1,7-bisfosfato.
  • Demostración de que el flujo de SHB17 aumenta con una alta demanda de ribosa, como durante la biogénesis del ribosoma.

Conclusiones:

  • La riboneogénesis representa una ruta distinta para la síntesis de ribosa-5-fosfato en la levadura.
  • SHB17 es una enzima crítica que compromete a la sedoheptulosa-1,7-bisfosfato para la riboneogénesis.
  • La actividad de esta vía está regulada por la demanda relativa de ribosa frente al NADPH.