败血症
炎症
生物
细胞生物学
自噬
NAD+激酶
烟酰胺腺嘌呤二核苷酸
医学
生物化学
烟酰胺单核苷酸
内科学
巨噬细胞
作者
Melinda Suchard,Dana Savulescu
出处
期刊:FEBS Journal
[Wiley]
日期:2021-03-29
卷期号:289 (4): 955-964
被引量:7
摘要
Divergent pathways of macrophage metabolism occur during infection, notably switching between oxidative phosphorylation and aerobic glycolysis (Warburg-like metabolism). Concurrently, macrophages shift between alternate and classical activation. A key enzyme upregulated in alternatively activated macrophages is indoleamine 2,3-dioxygenase, which converts tryptophan to kynurenine for de novo synthesis of nicotinamide. Nicotinamide can be used to replenish cellular NAD+ supplies. We hypothesize that an insufficient cellular NAD+ supply is the root cause of metabolic shifts in macrophages. We assert that manipulation of nicotinamide pathways may correct deleterious immune responses. We propose evaluation of nicotinamide (Vitamin B3) and analogues, including isoniazid, nicotinamide mononucleotide and nicotinamide riboside, as potential therapy for infectious causes of sepsis, including COVID-19.
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