Metal-dependent amoebic enzymes

Metal-dependent amoebic enzymes are a diverse group of proteins within protozoan parasites, most notably Entamoeba histolytica, that require divalent metal cations like iron (Fe2+), zinc (Zn2+), or magnesium (Mg2+) to function as catalytic cofactors (PubMed: 15612913). These enzymes play pivotal roles in the parasite's survival, including energy metabolism via iron-dependent alcohol dehydrogenase (EhADH2) and protection against oxidative stress through iron-superoxide dismutase (Fe-SOD) (PubMed: 10411745). The therapeutic strategy targeting these enzymes involves the use of luminal amebicides like iodoquinol and clioquinol, which act as chelating agents. By binding to essential metal ions in the intestinal lumen, these drugs deprive the parasite of the cofactors necessary for enzyme activity, effectively inhibiting metabolic processes and leading to the death of the trophozoites (StatPearls: NBK546644). This target is primarily relevant for treating asymptomatic carriers of E. histolytica or as a follow-up to systemic treatment for invasive amebiasis to ensure the clearance of luminal parasites. However, the use of drugs targeting this system is limited by potential neurotoxicity, such as subacute myelo-optic neuropathy (SMON) associated with clioquinol (PubMed: 11526243).

Other names

Amoebic metalloenzymesMetal-dependent enzymes of Entamoeba histolyticaEssential metal ions in intestinal lumenLuminal amebicide targets

Chelation of essential divalent metal ions (e.g., iron, zinc, copper) in the intestinal lumen, which deprives the parasite of necessary cofactors and inhibits the activity of metal-dependent enzymes essential for its survival (StatPearls: NBK546644).