The NADH effector pathway is a redox-sensitive regulatory network controlled by the Rex regulog, which enables bacterial cells to adapt gene expression in response to the cellular NADH/NAD⁺ ratio. Rex is a redox-sensing transcriptional repressor that binds DNA when NAD⁺ levels are high and dissociates upon NADH binding, thus activating transcription under reducing conditions. A key sensor among Gram-positive bacteria, Rex represses alternative respiratory gene expression until a limited oxygen supply elevates the intracellular NADH:NAD(+) ratio. Rex monitors the intracellular redox state and modulates the expression of genes involved in energy metabolism, respiration, and heme biosynthesis. When the NADH/NAD⁺ ratio increases—indicating a more reduced environment—Rex-mediated repression is lifted, allowing transcription of target genes that help restore redox balance. Key genes in the Rex regulog include: rex – Encodes the Rex transcriptional repressor itself, forming part of an autoregulatory feedback loop. hemA – Encodes glutamyl-tRNA reductase, initiating the heme biosynthesis pathway by producing glutamate-1-semialdehyde. hemB – Encodes porphobilinogen synthase, which catalyzes the condensation of two molecules of aminolevulinic acid (ALA) to form porphobilinogen. hemC – Encodes porphobilinogen deaminase, converting porphobilinogen into hydroxymethylbilane. hemD – Encodes uroporphyrinogen III synthase, forming the first macrocyclic intermediate in the heme biosynthetic pathway.

NADH References