BCKDHA

Branched chain keto acid dehydrogenase E1, alpha polypeptide
PDB rendering based on 1dtw.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1DTW​, 1OLS​, 1OLU​, 1OLX​, 1U5B​, 1V11​, 1V16​, 1V1M​, 1V1R​, 1WCI​, 1X7W​, 1X7X​, 1X7Y​, 1X7Z​, 1X80​, 2BEU​, 2BEV​, 2BEW​, 2BFB​, 2BFC​, 2BFD​, 2BFE​, 2BFF​, 2J9F​
Identifiers
Symbols	BCKDHA ; BCKDE1A; MSU; MSUD1; OVD1A
External IDs	OMIM: 608348 MGI: 107701 HomoloGene: 569 GeneCards: BCKDHA Gene
EC number	1.2.4.4
Gene ontology Molecular function • alpha-ketoacid dehydrogenase activity • 3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring) activity • protein binding • carboxy-lyase activity • metal ion binding Cellular component • mitochondrion • mitochondrial matrix • mitochondrial alpha-ketoglutarate dehydrogenase complex Biological process • branched-chain amino acid catabolic process • cellular nitrogen compound metabolic process • small molecule metabolic process • oxidation-reduction process Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	593	12039
Ensembl	ENSG00000248098	ENSMUSG00000060376
UniProt	P12694	Q3U3J1
RefSeq (mRNA)	NM_000709	NM_007533
RefSeq (protein)	NP_000700	NP_031559
Location (UCSC)	Chr 19: 41.4 – 41.43 Mb	Chr 7: 25.63 – 25.66 Mb
PubMed search

2-oxoisovalerate dehydrogenase subunit alpha, mitochondrial is an enzyme that in humans is encoded by the BCKDHA gene.^[1]

The second major step in the catabolism of the branched-chain amino acids, isoleucine, leucine, and valine, is catalyzed by the branched-chain alpha-keto acid dehydrogenase complex (BCKD; EC 1.2.4.4), an inner-mitochondrial enzyme complex that consists of 3 catalytic components: a heterotetrameric (alpha2, beta2) branched-chain alpha-keto acid decarboxylase (E1), a homo-24-meric dihydrolipoyl transacylase (E2; MIM 248610), and a homodimeric dihydrolipoamide dehydrogenase (E3; MIM 238331). The reaction is irreversible and constitutes the first committed step in BCAA oxidation. The complex also contains 2 regulatory enzymes, a kinase and a phosphorylase. The BCKDHA gene encodes the alpha subunit of E1, and the BCKDHB gene (MIM 248611) encodes the beta subunit of E1.[supplied by OMIM]^[1]

References

1. "Entrez Gene: BCKDHA branched chain keto acid dehydrogenase E1, alpha polypeptide".

Further reading

• Mitsubuchi H, Matsuda I, Nobukuni Y; et al. (1992). "Gene analysis of Mennonite maple syrup urine disease kindred using primer-specified restriction map modification". J. Inherit. Metab. Dis. 15 (2): 181–7. doi:10.1007/BF01799628. PMID 1356170.
• McKean MC, Winkeler KA, Danner DJ (1992). "Nucleotide sequence of the 5' end including the initiation codon of cDNA for the E1 alpha subunit of the human branched chain alpha-ketoacid dehydrogenase complex". Biochim. Biophys. Acta 1171 (1): 109–12. doi:10.1016/0167-4781(92)90149-t. PMID 1420356.
• Dariush N, Fisher CW, Cox RP, Chuang DT (1991). "Structure of the gene encoding the entire mature E1 alpha subunit of human branched-chain alpha-keto acid dehydrogenase complex (1991) FEBS Letters 284, 34-38". FEBS Lett. 291 (2): 376–7. doi:10.1016/0014-5793(91)81324-2. PMID 1682165.
• Eisenstein RS, Hoganson G, Miller RH, Harper AE (1991). "Altered phosphorylation state of branched-chain 2-oxo acid dehydrogenase in a branched-chain acyltransferase deficient human fibroblast cell line". J. Inherit. Metab. Dis. 14 (1): 37–44. doi:10.1007/BF01804386. PMID 1861457.
• Fisher CR, Fisher CW, Chuang DT, Cox RP (1991). "Occurrence of a Tyr393----Asn (Y393N) mutation in the E1 alpha gene of the branched-chain alpha-keto acid dehydrogenase complex in maple syrup urine disease patients from a Mennonite population". Am. J. Hum. Genet. 49 (2): 429–34. PMC 1683290. PMID 1867199.
• Fisher CR, Chuang JL, Cox RP; et al. (1991). "Maple syrup urine disease in Mennonites. Evidence that the Y393N mutation in E1 alpha impedes assembly of the E1 component of branched-chain alpha-keto acid dehydrogenase complex". J. Clin. Invest. 88 (3): 1034–7. doi:10.1172/JCI115363. PMC 295513. PMID 1885764.
• Zneimer SM, Lau KS, Eddy RL; et al. (1991). "Regional assignment of two genes of the human branched-chain alpha-keto acid dehydrogenase complex: the E1 beta gene (BCKDHB) to chromosome 6p21-22 and the E2 gene (DBT) to chromosome 1p31". Genomics 10 (3): 740–7. doi:10.1016/0888-7543(91)90458-Q. PMID 1889817.
• Zhang B, Zhao Y, Harris RA, Crabb DW (1991). "Molecular defects in the E1 alpha subunit of the branched-chain alpha-ketoacid dehydrogenase complex that cause maple syrup urine disease". Mol. Biol. Med. 8 (1): 39–47. PMID 1943689.
• Dariush N, Fisher CW, Cox RP, Chuang DT (1991). "Structure of the gene encoding the entire mature E1 alpha subunit of human branched-chain alpha-keto acid dehydrogenase complex". FEBS Lett. 284 (1): 34–8. doi:10.1016/0014-5793(91)80755-R. PMID 2060625.
• Matsuda I, Nobukuni Y, Mitsubuchi H; et al. (1990). "A T-to-A substitution in the E1 alpha subunit gene of the branched-chain alpha-ketoacid dehydrogenase complex in two cell lines derived from Menonite maple syrup urine disease patients". Biochem. Biophys. Res. Commun. 172 (2): 646–51. doi:10.1016/0006-291X(90)90723-Z. PMID 2241958.
• Zhang B, Edenberg HJ, Crabb DW, Harris RA (1989). "Evidence for both a regulatory mutation and a structural mutation in a family with maple syrup urine disease". J. Clin. Invest. 83 (4): 1425–9. doi:10.1172/JCI114033. PMC 303839. PMID 2703538.
• Fekete G, Plattner R, Crabb DW; et al. (1989). "Localization of the human gene for the El alpha subunit of branched chain keto acid dehydrogenase (BCKDHA) to chromosome 19q13.1----q13.2". Cytogenet. Cell Genet. 50 (4): 236–7. doi:10.1159/000132768. PMID 2805821.
• Fisher CW, Chuang JL, Griffin TA; et al. (1989). "Molecular phenotypes in cultured maple syrup urine disease cells. Complete E1 alpha cDNA sequence and mRNA and subunit contents of the human branched chain alpha-keto acid dehydrogenase complex". J. Biol. Chem. 264 (6): 3448–53. PMID 2914958.
• Zhang B, Crabb DW, Harris RA (1989). "Nucleotide and deduced amino acid sequence of the E1 alpha subunit of human liver branched-chain alpha-ketoacid dehydrogenase". Gene 69 (1): 159–64. doi:10.1016/0378-1119(88)90390-3. PMID 3224821.
• Hu CW, Lau KS, Griffin TA; et al. (1988). "Isolation and sequencing of a cDNA encoding the decarboxylase (E1)alpha precursor of bovine branched-chain alpha-keto acid dehydrogenase complex. Expression of E1 alpha mRNA and subunit in maple-syrup-urine-disease and 3T3-L1 cells". J. Biol. Chem. 263 (18): 9007–14. PMID 3379058.
• Chuang JL, Davie JR, Chinsky JM; et al. (1995). "Molecular and biochemical basis of intermediate maple syrup urine disease. Occurrence of homozygous G245R and F364C mutations at the E1 alpha locus of Hispanic-Mexican patients". J. Clin. Invest. 95 (3): 954–63. doi:10.1172/JCI117804. PMC 441427. PMID 7883996.
• Wynn RM, Kochi H, Cox RP, Chuang DT (1994). "Differential processing of human and rat E1 alpha precursors of the branched-chain alpha-keto acid dehydrogenase complex caused by an N-terminal proline in the rat sequence". Biochim. Biophys. Acta 1201 (1): 125–8. doi:10.1016/0304-4165(94)90161-9. PMID 7918575.
• Chuang JL, Fisher CR, Cox RP, Chuang DT (1994). "Molecular basis of maple syrup urine disease: novel mutations at the E1 alpha locus that impair E1(alpha 2 beta 2) assembly or decrease steady-state E1 alpha mRNA levels of branched-chain alpha-keto acid dehydrogenase complex". Am. J. Hum. Genet. 55 (2): 297–304. PMC 1918348. PMID 8037208.
• Nobukuni Y, Mitsubuchi H, Hayashida Y; et al. (1993). "Heterogeneity of mutations in maple syrup urine disease (MSUD): screening and identification of affected E1 alpha and E1 beta subunits of the branched-chain alpha-keto-acid dehydrogenase multienzyme complex". Biochim. Biophys. Acta 1225 (1): 64–70. doi:10.1016/0925-4439(93)90123-i. PMID 8161368.
• Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.