Myo-inositol oxygenase (MIOX)

Myo-inositol oxygenase (MIOX) is a non-heme diiron enzyme primarily expressed in the kidney that catalyzes the oxidation of myo-inositol to glucuronic acid, the first step in the only known pathway for inositol catabolism in mammals[1][2][3]. MIOX employs a unique four-electron transfer at the catalytic site, converting myo-inositol into glucuronic acid, which subsequently enters the glucuronate-xylulose and pentose phosphate pathways for cellular metabolism[1]. The structure of MIOX belongs to the HD-domain superfamily and features a monomeric 33 kDa protein core with a distinctive diiron center, deeply buried to limit damage from reactive intermediates[1][2]. It is a key enzyme in kidney function and in regulating systemic inositol homeostasis. MIOX activity and expression are tightly controlled and implicated in pathological states such as diabetic nephropathy and acute kidney injury, where MIOX upregulation is associated with increased oxidative stress and tissue injury[1][2]. Current therapeutic interest focuses on inhibiting MIOX activity to potentially ameliorate diabetic complications and its utility as a biomarker for kidney injury[1][2][3].

Other names

Inositol oxygenaseALDRL6KSP32RSORMI oxygenaseAldehyde reductase-like 6Kidney-specific protein 32Renal-specific oxidoreductasealdose reductase like 6

For inhibitors, competitive inhibition at the diiron cluster; blockade of substrate access or catalysis by interfering with active site or substrate binding (e.g., myo-inosose-1)