Interferon-stimulated gene products as regulators of central carbon metabolism,The FEBS Journal

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Interferon-stimulated gene products as regulators of central carbon metabolism
The FEBS Journal ( IF 5.5 ) Pub Date : 2020-11-13 , DOI: 10.1111/febs.15625
Kourosh H Ebrahimi ₁ , Javier Gilbert-Jaramillo _{2,

3} , William S James ₂ , James S O McCullagh ₁

Affiliation

In response to viral infections, the innate immune system rapidly activates expression of several interferon-stimulated genes (ISGs), whose protein and metabolic products are believed to directly interfere with the viral life cycle. Here, we argue that biochemical reactions performed by two specific protein products of ISGs modulate central carbon metabolism to support a broad-spectrum antiviral response. We demonstrate that the metabolites generated by metalloenzymes nitric oxide synthase and the radical S-adenosylmethionine (SAM) enzyme RSAD2 inhibit the activity of the housekeeping and glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH). We discuss that this inhibition is likely to stimulate a range of metabolic and signalling processes to support a broad-spectrum immune response. Based on these analyses, we propose that inhibiting GAPDH in individuals with deteriorated cellular innate immune response like elderly might help in treating viral diseases such as COVID-19.

中文翻译：

干扰素刺激的基因产物作为中央碳代谢的调节剂

作为对病毒感染的反应，先天免疫系统会迅速激活几种干扰素刺激基因 (ISG) 的表达，这些基因的蛋白质和代谢产物被认为会直接干扰病毒的生命周期。在这里，我们认为由 ISG 的两种特定蛋白质产物进行的生化反应调节中心碳代谢以支持广谱抗病毒反应。我们证明金属酶一氧化氮合酶和自由基 S-腺苷甲硫氨酸 (SAM) 酶 RSAD2 产生的代谢物抑制管家和糖酵解酶甘油醛 3-磷酸脱氢酶 (GAPDH) 的活性。我们讨论了这种抑制可能会刺激一系列代谢和信号传导过程以支持广谱免疫反应。基于这些分析，

更新日期：2020-11-13

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