Succinyl-CoA ligase DP-formingsubunit alpha, mitochondrial is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different molecule ...

that in humans is encoded by the ''SUCLG1''

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

Structure

The enzyme encoded by SUCLG1 can exist in either a

phosphorylated In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...

form or a dephosphorylated form. In the dephosphorylated structure, a phosphate ion works in coordination with a

histidine Histidine (symbol His or H) is an essential amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated –NH3+ form under biological conditions), a carboxylic acid group (which is in the ...

residue in the active site and the two alpha helices, one contributed by each subunit of the alphabeta-dimer to stabilize the structure. One of the alpha helices contains amino acids, the modification of which result in conformational changes that accommodate either the bound

phosphoryl {{unreferenced, date=May 2015 A phosphoryl group is the chemical ion or radical: P+O32−, containing phosphorus and oxygen. (The correct chemical name for this −PO32− group is phosphonato, and phosphono for −PO3H2; as ''phosphoryl'' in ch ...

group or the free phosphate ion.

Function

This gene encodes the alpha subunit of the

heterodimeric In biochemistry, a protein dimer is a macromolecular complex formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ''dimer'' has ...

enzyme

succinate Succinic acid () is a dicarboxylic acid with the chemical formula (CH2)2(CO2H)2. The name derives from Latin ''succinum'', meaning amber. In living organisms, succinic acid takes the form of an anion, succinate, which has multiple biological ro ...

coenzyme A ligase. This enzyme is targeted to the mitochondria and catalyzes the conversion of

succinyl CoA Succinyl-coenzyme A, abbreviated as succinyl-CoA () or SucCoA, is a thioester of succinic acid and coenzyme A. Sources It is an important intermediate in the citric acid cycle, where it is synthesized from α-ketoglutarate by α-ketoglutarate deh ...

and ADP or GDP to succinate and ATP or GTP. Mutations in this gene are the cause of the metabolic disorder fatal infantile

lactic acidosis Lactic acidosis is a medical condition characterized by a build-up of lactate (especially -lactate) in the body, with formation of an excessively low pH in the bloodstream. It is a form of metabolic acidosis, in which excessive acid accumulates d ...

and mitochondrial DNA depletion.

Clinical significance

Succinate-CoA ligase deficiency is responsible for encephalomyopathy with mitochondrial DNA depletion and mild methylmalonic aciduria. Mutations in SUCLG1 lead to complete absence of SUCLG1 protein and are responsible for a very severe disorder with

antenatal Prenatal development () includes the development of the embryo and of the fetus during a viviparous animal's gestation. Prenatal development starts with fertilization, in the germinal stage of embryonic development, and continues in fetal devel ...

manifestations. Furthermore, it is shown that in the absence of SUCLG1 protein, no SUCLA2 protein is found in

fibroblasts A fibroblast is a type of biological cell that synthesizes the extracellular matrix and collagen, produces the structural framework ( stroma) for animal tissues, and plays a critical role in wound healing. Fibroblasts are the most common cells ...

by western blot analysis. This result is consistent with a degradation of SUCLA2 when its heterodimer partner, SUCLG1, is absent. As mitochondrial DNA depletion in muscle is not a constant finding in SUCLG1 patients, diagnosis should not be based on it; additionally, it may be that alternative physiopathological mechanisms may be considered to explain the combined

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

Structure

Function

Clinical significance

Interactive pathway map

References

Further reading

External links