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Other Fe-dependent enzymes

Molecular classification
Enzyme, Oxidoreductase, Iron-dependent enzyme
01

Overview

Other Fe-dependent enzymes refers to a diverse group of enzymes that utilize iron as a critical cofactor for their catalytic activity, typically excluding the well-characterized Cytochrome P450 family. This group encompasses both heme-containing enzymes, such as cyclooxygenases, and non-heme iron enzymes, including prolyl hydroxylases and ribonucleotide reductase. These enzymes are integral to fundamental biological processes such as DNA replication, oxygen sensing, neurotransmitter biosynthesis, and lipid metabolism. For example, ribonucleotide reductase is essential for producing deoxyribonucleotides for DNA synthesis, making it a significant target in oncology. Prolyl hydroxylases regulate the stability of hypoxia-inducible factors (HIF), serving as therapeutic targets for treating anemia and ischemic conditions. Drugs targeting these enzymes often function by chelating the catalytic iron or competing with substrates at the active site. Because iron is ubiquitous in biological systems, therapeutic strategies targeting this class must achieve high specificity to avoid systemic iron-related toxicities or the unintended inhibition of other vital iron-dependent pathways.

Other names
Non-heme iron-dependent enzymesIron-containing enzymes (excluding CYPs)Fe-dependent oxidoreductasesIron-dependent dioxygenases
02

Mechanism of action

Inhibition of enzyme activity through iron chelation, competitive inhibition at the iron-binding active site, or stabilization of the enzyme-substrate complex to prevent catalytic turnover.

03

Biological functions

DNA synthesisOxygen sensingLipid metabolismNeurotransmitter synthesisCollagen synthesisHypoxia response
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Disease associations

CancerAnemiaInflammationHypertensionMetabolic disordersNeurodegenerative disease
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Safety considerations

Systemic iron deficiencyOff-target inhibition of essential metalloenzymesToxicity from iron chelationCardiovascular risks (associated with HIF-PH inhibitors)Gastrointestinal distress
06

Interacting drugs

Hydroxyurea

7 more in the full profile.

07

Biomarkers

Hemoglobin levelsLeukotriene levelsCatecholamine levelsHIF-1alpha levelsSerum ferritin

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