ETHE1
Template:Short description Template:Cs1 configTemplate:Infobox gene Protein ETHE1, mitochondrial, also known as "ethylmalonic encephalopathy 1 protein" and "per sulfide dioxygenase", is a protein that in humans is encoded by the ETHE1 gene located on chromosome 19.[1]
Structure
The human ETHE1 gene consists of 7 exons and encodes for a protein that is approximately 27 kDa in size.
Function
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.[1]
The ETHE1 protein is thought to localize primarily to the mitochondrial matrix[2][3] 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 sulfite + 2 H+ (overall reaction)
- (1a) glutathione + sulfur S-sulfanylglutathione (glutathione persulfide, spontaneous reaction)
- (1b) S-sulfanylglutathione + O2 + H2O glutathione + sulfite + 2 H+[2]
and requires iron[4] and possibly glutathione[4] as cofactors. The physiological substrate of ETHE1 is thought to be glutathione persulfide,[4] an intermediate metabolite involved in hydrogen sulfide degradation.
Clinical significance
Mutations in ETHE1 gene are thought to cause ethylmalonic encephalopathy,[3][5] 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.[4] Mouse models of Ethe1 genetic ablation likewise exhibited reduced sulfide dioxygenase catabolism and cranial features of ethylmalonic encephalopathy.[2] Decrease in sulfide dioxygenase activity results in abnormal catabolism of hydrogen sulfide, a gas-phase signaling molecule in the central nervous system,[4] whose accumulation is thought to inhibit cytochrome c oxidase activity in the respiratory chain of the mitochondrion.[2] However, other metabolic pathways may also be involved that could exert a modulatory effect on hydrogen sulfide toxicity.[6]
Interactions
ETHE1 has been shown to interact with RELA.[7]