Iron-regulated enzyme

Iron-regulated enzymes encompass a diverse group of metalloproteins, including those with heme, iron-sulfur (Fe-S) clusters, or direct iron binding, whose expression and function are tightly controlled by iron regulatory proteins (IRP1 and IRP2) that sense cytosolic iron levels via interactions with iron-responsive elements (IREs) in target mRNAs. Under low iron conditions, IRPs stabilize mRNAs for iron uptake proteins like transferrin receptor 1 (TfR1) and divalent metal transporter 1 (DMT1) while repressing storage proteins like ferritin; high iron reverses this to favor storage and limit uptake. These enzymes perform essential roles in oxygen transport (e.g., hemoglobin, myoglobin), energy production (e.g., cytochromes in the electron transport chain), DNA synthesis (e.g., ribonucleotide reductase), detoxification (e.g., catalase, cytochrome P450), and immune defense (e.g., myeloperoxidase, nitric oxide synthase). Dysregulation contributes to iron overload diseases like hereditary hemochromatosis, where excess iron promotes oxidative damage via reactive oxygen species (ROS) generation, inflammation during infection by sequestering iron from pathogens, and cancer proliferation due to heightened iron needs. No specific drugs directly target these enzymes as a class; instead, iron homeostasis modulators like hepcidin analogs affect upstream regulators such as ferroportin. This regulatory network ensures iron availability for catalysis while preventing toxicity, linking iron sensing to metabolism, immunity, and disease pathology.

Other names

IRE/IRP-regulated enzymesIron-responsive enzymes