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Updated: Jan 12, 2026

Nucleoside Triphosphates - From Synthesis to Biochemical Characterization

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Published on: April 3, 2014

NUDT5 regula el metabolismo de la purina y la sensibilidad a la tiopurina mediante la interacción con PPAT

Zheng Wu¹, Phong T Nguyen¹, Varun Sondhi^1,2

¹Children's Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.

Science (New York, N.Y.)

|November 6, 2025

Resumen

Nudix hidrolasa 5 (NUDT5) regula la biosíntesis de purinas de novo (DNPB) mediante la interacción con el PPAT. Esta interacción suprime el DNPB durante el rescate de purina, manteniendo el equilibrio celular de purina e influyendo en la resistencia a los fármacos de tiopurina.

Área de la Ciencia:

El metabolismo celular
La bioquímica
Biología molecular

Sus antecedentes:

Las células sintetizan nucleótidos de purina a través de la biosíntesis de purina de novo (DNPB) y las vías de salvamento de purina.
El rescate de purinas normalmente reprime el DNPB, pero los mecanismos subyacentes no se comprenden completamente.

Objetivo del estudio:

Identificar los reguladores de la biosíntesis de las purinas de novo (DNPB).
Para aclarar el mecanismo por el cual el rescate de purinas suprime DNPB.

Principales métodos:

Se investigó el papel de Nudix hidrolasa 5 (NUDT5) en la regulación de la DNPB.
Se examinó la interacción entre NUDT5 y la fosforibosil pirofosfato amidotransferasa (PPAT).
Se evaluó el impacto de la interacción NUDT5-PPAT en la actividad enzimática de PPAT y el desmontaje de los purinosomas.

Principales resultados:

NUDT5 fue identificado como un regulador clave de DNPB.
NUDT5 suprime DNPB durante el rescate de purinas a través de la interacción con PPAT, independientemente de su actividad catalítica.
La interacción NUDT5-PPAT inhibe la actividad de PPAT y desmonta el purinosoma.
La alteración de la interacción NUDT5-PPAT dio lugar a una resistencia excesiva al DNPB y a la tiopurina.

Conclusiones:

NUDT5 juega un papel crítico en el equilibrio de las vías de salvamento de DNPB y purinas.
La interacción NUDT5-PPAT es crucial para mantener la homeostasis de los nucleótidos purinos celulares.
Dirigirse a la interacción NUDT5-PPAT puede ofrecer estrategias para superar la resistencia a la tiopurina.

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