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.
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.
The ETHE1 protein is thought to localize primarily to the
mitochondrial matrix and functions as a
sulfur dioxygenase
Sulfur dioxygenase (, ''sulfur oxygenase'', ''sulfur:oxygen oxidoreductase'') is an enzyme with systematic name ''S-sulfanylglutathione:oxygen oxidoreductase''. This enzyme catalyses the following chemical reaction
: sulfur + O2 + H2O \rightleft ...
. Sulfur deoxygenates are proteins that function in
sulfur metabolism. The ETHE1 protein is thought to catalyze the following reaction:
:
sulfur
Sulfur (or sulphur in British English) is a chemical element with the symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms form cyclic octatomic molecules with a chemical formula ...
+ O
2 + H
2O
sulfite
Sulfites or sulphites are compounds that contain the sulfite ion (or the sulfate(IV) ion, from its correct systematic name), . The sulfite ion is the conjugate base of bisulfite. Although its acid ( sulfurous acid) is elusive, its salts are wide ...
+ 2 H
+ (overall reaction)
: (1a)
glutathione + sulfur
S-sulfanylglutathione (glutathione persulfide, spontaneous reaction)
: (1b) S-sulfanylglutathione + O
2 + H
2O
glutathione + sulfite + 2 H
+
and requires
iron and possibly
glutathione as
cofactors. The physiological
substrate
Substrate may refer to:
Physical layers
*Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached
** Substrate (locomotion), the surface over which an organism lo ...
of ETHE1 is thought to be
glutathione persulfide,
an intermediate
metabolite
In biochemistry, a metabolite is an intermediate or end product of metabolism.
The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, c ...
involved in
hydrogen sulfide
Hydrogen sulfide is a chemical compound with the formula . It is a colorless chalcogen-hydride gas, and is poisonous, corrosive, and flammable, with trace amounts in ambient atmosphere having a characteristic foul odor of rotten eggs. The unde ...
degradation.
Clinical significance
Mutations in ETHE1
gene are thought to cause
ethylmalonic encephalopathy,
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.
Mouse models of Ethe1 genetic ablation likewise exhibited reduced sulfide dioxygenase catabolism and cranial features of ethylmalonic encephalopathy.
Decrease in sulfide dioxygenase activity results in abnormal
catabolism
Catabolism () is the set of metabolic pathways that breaks down molecules into smaller units that are either oxidized to release energy or used in other anabolic reactions. Catabolism breaks down large molecules (such as polysaccharides, lipids, ...
of
hydrogen sulfide
Hydrogen sulfide is a chemical compound with the formula . It is a colorless chalcogen-hydride gas, and is poisonous, corrosive, and flammable, with trace amounts in ambient atmosphere having a characteristic foul odor of rotten eggs. The unde ...
, a gas-phase signaling molecule in the central nervous system,
whose accumulation is thought to inhibit
cytochrome c oxidase activity in the
respiratory chain of the
mitochondrion
A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is used ...
.
However, other metabolic pathways may also be involved that could exert a modulatory effect on
hydrogen sulfide
Hydrogen sulfide is a chemical compound with the formula . It is a colorless chalcogen-hydride gas, and is poisonous, corrosive, and flammable, with trace amounts in ambient atmosphere having a characteristic foul odor of rotten eggs. The unde ...
toxicity.
Interactions
ETHE1 has been shown to
interact with
RELA.
References
Further reading
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Genes
Human proteins
{{gene-19-stub