HADHA
Protein-coding gene in the species Homo sapiens
From Wikipedia, the free encyclopedia
Trifunctional enzyme subunit alpha, mitochondrial also known as hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), alpha subunit is a protein that in humans is encoded by the HADHA gene. Mutations in HADHA have been associated with trifunctional protein deficiency or long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency.[5]
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| Aliases | HADHA, hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase (trifunctional protein), alpha subunit, ECHA, GBP, HADH, LCEH, LCHAD, MTPA, TP-ALPHA, hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 600890; MGI: 2135593; HomoloGene: 152; GeneCards: HADHA; OMA:HADHA - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Structure
HADHA is an 82.9 kDa protein composed of 763 amino acids.[6][7]
The mitochondrial membrane-bound heterocomplex is composed of four alpha and four beta subunits, with the alpha subunit catalyzing the 3-hydroxyacyl-CoA dehydrogenase and enoyl-CoA hydratase activities. The genes of the alpha and beta subunits of the mitochondrial trifunctional protein are located adjacent to each other in the human genome in a head-to-head orientation.[5]
Function
This gene encodes the alpha subunit of the mitochondrial trifunctional protein, which catalyzes the last three steps of mitochondrial beta-oxidation of long chain fatty acids.[5] The enzyme converts medium- and long-chain 2-enoyl-CoA compounds into the following 3-ketoacyl-CoA when NAD is solely present, and acetyl-CoA when NAD and CoASH are present.[8] The alpha subunit catalyzes this reaction, and is attached to HADHB, which catalyzes the last step of the reaction.[9]
Clinical significance
Mutations in this gene result in trifunctional protein deficiency or long-chain 3-hydroxyacyl-coenzyme A dehydrogenase deficiency.[5]
The most common form of the mutation is G1528C, in which the guanine at the 1528th position is changed to a cytosine. The gene mutation creates a protein deficiency that is associated with impaired oxidation of long-chain fatty acids that can lead to sudden infant death.[10] Clinical manifestations of this deficiency can include myopathy, cardiomyopathy, episodes of coma, and hypoglycemia.[11] Long-chain L-3-hydroxyacyl-coenzyme A dehydrogenase deficiency is associated with some pregnancy-specific disorders, including preeclampsia, HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), hyperemesis gravidarum,[12][13] acute fatty liver of pregnancy,[14] and maternal floor infarct of the placenta.[12][13]
From a clinical perspective, HADHA might also be a useful marker to predict resistance to certain types of chemotherapy in patients with lung cancer.[15]
Interactions
HADHA has been shown to have 142 binary protein-protein interactions including 117 co-complex interactions. HADHA appears to interact with GABARAP, MAP1LC3B, TRAF6, GABARAPL2, GABARAPL1, GAST, BCAR3, EPB41, TNFRSF1A, HLA-B, NFKB2, MAP3K1, IKBKE, PRKAB1, RIPK3, CD74, NR4A1, cdsA, mtaD, ATXN2L, ABCF2, and MAPK3.[16]
