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 mainly in the gastrointestinal tract, but also in several other tissues such as the liver and 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, a 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]