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Nicotinamide pathways as the root cause of sepsis – an evolutionary perspective on macrophage energetic shifts
Author(s) -
Suchard Melinda S.,
Savulescu Dana M.
Publication year - 2022
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.15807
Subject(s) - nicotinamide mononucleotide , nicotinamide , nad+ kinase , niacinamide , indoleamine 2,3 dioxygenase , niacin , metabolic pathway , kynurenine , glycolysis , biochemistry , chemistry , macrophage , nicotinamide adenine dinucleotide , nicotinamide phosphoribosyltransferase , kynurenine pathway , metabolism , biology , microbiology and biotechnology , enzyme , tryptophan , amino acid , in vitro
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.