HADHA Mitochondrial trifunctional enzyme catalyzes the last three of the four reactions of the mitochondrial beta-oxidation pathway. The mitochondrial beta-oxidation pathway is the major energy-producing process in tissues and is performed through four consecutive reactions breaking down fatty acids into acetyl-CoA. Among the enzymes involved in this pathway, the trifunctional enzyme exhibits specificity for long-chain fatty acids. Mitochondrial trifunctional enzyme is a heterotetrameric complex composed of two proteins, the trifunctional enzyme subunit alpha/HADHA described here carries the 2,3-enoyl-CoA hydratase and the 3-hydroxyacyl-CoA dehydrogenase activities while the trifunctional enzyme subunit beta/HADHB bears the 3-ketoacyl-CoA thiolase activity. Independently of the subunit beta, the trifunctional enzyme subunit alpha/HADHA also has a monolysocardiolipin acyltransferase activity. It acylates monolysocardiolipin into cardiolipin, a major mitochondrial membrane phospholipid which plays a key role in apoptosis and supports mitochondrial respiratory chain complexes in the generation of ATP. Allows the acylation of monolysocardiolipin with different acyl-CoA substrates including oleoyl-CoA for which it displays the highest activity. In the central section; belongs to the 3-hydroxyacyl-CoA dehydrogenase family. 2 alternatively spliced human isoforms have been reported. Note: This description may include information from UniProtKB.
Protein type: Acetyltransferase; Amino Acid Metabolism - lysine degradation; Amino Acid Metabolism - tryptophan; Amino Acid Metabolism - valine, leucine and isoleucine degradation; Carbohydrate Metabolism - butanoate; Carbohydrate Metabolism - propanoate; EC; EC; Lipid Metabolism - fatty acid; Lipid Metabolism - fatty acid elongation in mitochondria; Lipid Metabolism - unsaturated fatty acid biosynthesis; Lyase; Mitochondrial; Other Amino Acids Metabolism - beta-alanine; Oxidoreductase; Secondary Metabolites Metabolism - limonene and pinene degradation
Chromosomal Location of mouse Ortholog: 5|5 B1
Cellular Component:  mitochondrial fatty acid beta-oxidation multienzyme complex; mitochondrial nucleoid; mitochondrion
Molecular Function:  3-hydroxyacyl-CoA dehydrogenase activity; acetyl-CoA C-acyltransferase activity; catalytic activity; enoyl-CoA hydratase activity; fatty-acyl-CoA binding; long-chain-3-hydroxyacyl-CoA dehydrogenase activity; long-chain-enoyl-CoA hydratase activity; lyase activity; NAD binding; oxidoreductase activity; protein-containing complex binding
Biological Process:  fatty acid beta-oxidation; fatty acid metabolic process; lipid metabolic process; metabolic process; oxidation-reduction process; response to drug; response to insulin
Reference #:  Q8BMS1 (UniProtKB)
Alt. Names/Synonyms: C77020; ECHA; Hadha; hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha; hydroxyacyl-Coenzyme A dehydrogenase/3-ketoacyl-Coenzyme A thiolase/enoyl-Coenzyme A hydratase (trifunctional protein), alpha subunit; Long chain 3-hydroxyacyl-CoA dehydrogenase; Long-chain enoyl-CoA hydratase; Monolysocardiolipin acyltransferase; Mtpa; OTTMUSP00000029769; TP-alpha; Trifunctional enzyme subunit alpha, mitochondrial
Gene Symbols: Hadha
Molecular weight: 82,670 Da
Basal Isoelectric point: 9.24  Predict pI for various phosphorylation states
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Protein Structure Not Found.

Cross-references to other databases:  AlphaFold  |  STRING  |  Reactome  |  BioGPS  |  Pfam  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene