Physiological vitamin- and iron-dependent pathways

Physiological vitamin- and iron-dependent pathways refer to a broad class of biochemical processes mediated by enzymes that require iron (Fe2+) and vitamins (most notably Vitamin C/ascorbate) as essential cofactors. The most prominent members of this group are the 2-oxoglutarate-dependent dioxygenases (2-OGDDs), which include prolyl hydroxylases involved in collagen synthesis and the regulation of hypoxia-inducible factors (HIF). These pathways are critical for maintaining the structural integrity of connective tissues, sensing cellular oxygen levels, and regulating epigenetic modifications such as DNA and histone demethylation. Vitamin C is typically required to maintain the iron cofactor in its active ferrous state, preventing enzyme inactivation during the catalytic cycle. Dysregulation of these pathways is linked to conditions like scurvy, anemia, and various cancers. Therapeutic interventions often involve supplementing cofactors to restore enzyme function or using small-molecule inhibitors to modulate specific signaling outcomes, such as stimulating erythropoiesis in chronic kidney disease.

Other names

2-oxoglutarate-dependent dioxygenase pathwaysIron- and ascorbate-dependent enzymatic pathwaysFe(II)/2-oxoglutarate-dependent oxygenase pathwaysAscorbate-dependent hydroxylase pathways

Modulation of enzyme activity through cofactor supplementation (iron, vitamin C), chelation of iron to inhibit activity, or competitive inhibition of 2-oxoglutarate binding sites to regulate downstream signaling (e.g., HIF stabilization).