Protein ETHE1, mitochondrial, also known as "ethylmalonic encephalopathy 1 protein" and "per sulfide dioxygenase", is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''ETHE1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

located on chromosome 19.

Structure

The human ETHE1

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 In the mitochondrion, the matrix is the space within the inner membrane. It can also be referred as the mitochondrial fluid. The word "matrix" stems from the fact that this space is viscous, compared to the relatively aqueous cytoplasm. The mitoc ...

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 Sulfur ( Americ ...

. Sulfur deoxygenates are proteins that function in

sulfur metabolism Sulfur is metabolized by all organisms, from bacteria and archaea to plants and animals. Sulfur can have an oxidation state from −2 to +6 and is reduced or oxidized by a diverse range of organisms. The element is present in proteins, sulfate est ...

. The ETHE1 protein is thought to catalyze the following reaction: :

sulfur Sulfur ( American spelling and the preferred IUPAC name) or sulphur ( Commonwealth spelling) is a chemical element; it has symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms ...

+ O₂ + H₂O

\rightleftharpoons

sulfite Sulfites or sulphites are compounds that contain the sulfite ion (systematic name: sulfate(IV) ion), . The sulfite ion is the conjugate base of bisulfite. Although its acid (sulfurous acid) is elusive, its salts are widely used. Sulfites are ...

+ 2 H⁺ (overall reaction) : (1a)

glutathione Glutathione (GSH, ) is an organic compound with the chemical formula . It is an antioxidant in plants, animals, fungi, and some bacteria and archaea. Glutathione is capable of preventing damage to important cellular components caused by sources ...

+ sulfur

\rightleftharpoons

S-sulfanylglutathione (glutathione persulfide, spontaneous reaction) : (1b) S-sulfanylglutathione + O₂ + H₂O

\rightleftharpoons

glutathione + sulfite + 2 H⁺ and requires

iron Iron is a chemical element; it has symbol Fe () and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, forming much of Earth's o ...

and possibly

cofactors Cofactor may also refer to: * Cofactor (biochemistry), a substance that needs to be present in addition to an enzyme for a certain reaction to be catalysed * A domain parameter in elliptic curve cryptography, defined as the ratio between the order ...

. 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 (aquatic environment), the earthy material that exi ...

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 toxic, corrosive, and flammable. Trace amounts in ambient atmosphere have a characteristic foul odor of rotten eggs. Swedish chemist ...

degradation.

Clinical significance

Mutations in ETHE1

are thought to cause

ethylmalonic encephalopathy Ethylmalonic encephalopathy (EE) is a rare autosomal recessive inborn error of metabolism. Patients affected with EE are typically identified shortly after birth, with symptoms including diarrhea, petechiae and seizures. The genetic defect in EE ...

, a rare

inborn error of metabolism Inborn errors of metabolism form a large class of genetic diseases involving congenital disorders of enzyme activities. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances (substrat ...

. 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, lipid ...

, a gas-phase signaling molecule in the central nervous system, whose accumulation is thought to inhibit

cytochrome c oxidase The enzyme cytochrome c oxidase or Complex IV (was , now reclassified as a translocasEC 7.1.1.9 is a large transmembrane protein complex found in bacteria, archaea, and the mitochondria of eukaryotes. It is the last enzyme in the Cellular respir ...

activity in the

respiratory chain An electron transport chain (ETC) is a series of protein complexes and other molecules which transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples this ...

of the

mitochondrion A mitochondrion () is an organelle found in the cell (biology), cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double lipid bilayer, membrane structure and use aerobic respiration to generate adenosine tri ...

. However, other metabolic pathways may also be involved that could exert a modulatory effect on

toxicity.

Interactions

ETHE1 has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...

with

RELA Transcription factor p65 also known as nuclear factor NF-kappa-B p65 subunit is a protein that in humans is encoded by the ''RELA'' gene. RELA, also known as p65, is a REL-associated protein involved in NF-κB heterodimer formation, nuclear tra ...

Structure

Function

Clinical significance

Interactions

References

Further reading