IDI1 Human

Isopentenyl-Diphosphate Delta Isomerase 1 (IDI1) is a crucial enzyme in the biosynthesis of isoprenoids, which are essential components in various biological processes. This enzyme catalyzes the conversion of isopentenyl diphosphate (IPP) to dimethylallyl diphosphate (DMAPP), a key step in the mevalonate pathway and the methylerythritol phosphate (MEP) pathway .

IDI1 belongs to the family of isomerases, specifically intramolecular oxidoreductases that transpose C=C bonds. The enzyme facilitates the isomerization of IPP to DMAPP through an antarafacial transposition of hydrogen. This reaction involves a protonation/deprotonation mechanism, resulting in a transient carbocation intermediate .

The active form of IDI1 is a monomer with alternating α-helices and β-sheets. The active site is deeply buried within the enzyme and consists of a glutamic acid residue and a cysteine residue. These residues interact with opposite sides of the IPP substrate, consistent with the antarafacial stereochemistry of isomerization .

IDI1 is peroxisomally localized and plays a vital role in the interconversion of IPP to DMAPP. This conversion is crucial for the synthesis of farnesyl diphosphate and ultimately cholesterol. Deficiencies in IDI1 activity have been observed in peroxisomal disorders such as Zellweger syndrome and neonatal adrenoleukodystrophy .

The IDI1 gene is located on chromosome 10 (10p15.3) and is associated with several pathways, including the superpathway of cholesterol biosynthesis and metabolism of steroids. It is a protein-coding gene with various aliases such as IPP Isomerase 1 and Isopentenyl Pyrophosphate Isomerase 1 .