ETHE1

The human ETHE1 gene consists of 7 exons and encodes for a protein that is approximately 27 kDa in size.

This gene encodes a protein that is expressed in the thyroid.[5]

The ETHE1 protein is thought to localize primarily to the mitochondrial matrix [6][7] and functions as a sulfur dioxygenase. Sulfur deoxygenates are proteins that function in sulfur metabolism. The ETHE1 protein is thought to catalyze the following reaction:

sulfur + O₂ + H₂O ${\displaystyle \rightleftharpoons }$ sulfite + 2 H⁺ (overall reaction)

(1a) glutathione + sulfur ${\displaystyle \rightleftharpoons }$ S-sulfanylglutathione (glutathione persulfide, spontaneous reaction)

(1b) S-sulfanylglutathione + O₂ + H₂O ${\displaystyle \rightleftharpoons }$ glutathione + sulfite + 2 H⁺[6]

and requires iron[8] and possibly glutathione[8] as cofactors. The physiological substrate of ETHE1 is thought to be glutathione persulfide,[8] an intermediate metabolite involved in hydrogen sulfide degradation.

Mutations in ETHE1 gene are thought to cause ethylmalonic encephalopathy,[7][9] a rare inborn error of metabolism. Patients carrying ETHE1 mutations have been found to exhibit lower activity of ETHE1 and affinity for the ETHE1 substrate.[8] Mouse models of Ethe1 genetic ablation likewise exhibited reduced sulfide dioxygenase catabolism and cranial features of ethylmalonic encephalopathy.[6] Decrease in sulfide dioxygenase activity results in abnormal catabolism of hydrogen sulfide, an gas-phase signaling molecule in the central nervous system,[8] whose accumulation is thought to inhibit cytochrome c oxidase activity in the respiratory chain of the mitochondrion.[6] However, other metabolic pathways may also be involved that could exert a modulatory effect on hydrogen sulfide toxicity.[10]

ETHE1 has been shown to interact with RELA.[11]