Wikipedia

Branched chain amino acid transaminase 1

Branched chain amino acid transaminase 1 is a protein that in humans is encoded by the BCAT1 gene.[5] It is the first enzyme in the branched-chain amino acid (BCAA) degradation pathway and facilitates the reversible transamination of BCAAs and glutamate. BCAT1 resides in the cytoplasm, while its isoform, BCAT2, is found in the mitochondria.

BCAT1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesBCAT1, BCATC, BCT1, ECA39, MECA39, PNAS121, PP18, branched chain amino acid transaminase 1
External IDsOMIM: 113520; MGI: 104861; HomoloGene: 20320; GeneCards: BCAT1; OMA:BCAT1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

586

12035

Ensembl

ENSG00000060982

ENSMUSG00000030268

UniProt

P54687

P24288

RefSeq (mRNA)

NM_001178091
NM_001178092
NM_001178093
NM_001178094
NM_005504

NM_001024468
NM_007532

RefSeq (protein)

NP_001171562
NP_001171563
NP_001171564
NP_001171565
NP_005495

NP_001019639
NP_031558

Location (UCSC)Chr 12: 24.81 – 24.95 MbChr 6: 144.94 – 145.02 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Function

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This gene encodes the cytosolic form of the enzyme branched-chain amino acid transaminase. This enzyme catalyzes the reversible transamination of branched-chain alpha-keto acids (BCKAs) to the branched-chain amino acids (BCAAs) valine, leucine and isoleucine, which are essential for cell growth. In humans, its primary role is the deamination of BCAAs, as humans lack the enzymes for de novo synthesis of BCKAs. The respective cosubstrates are alpha-ketoglutarate and glutamate. The respective reactions are:[6]

L-leucine + 2-oxoglutarate = 4-methyl-2-oxopentanoate + L-glutamate
L-isoleucine + 2-oxoglutarate = (S)-3-methyl-2-oxopentanoate + L-glutamate
L-valine + 2-oxoglutarate = 3-methyl-2-oxobutanoate + L-glutamate

Cells can further degrade BCKAs by the branched-chain keto acid dehydrogenase complex from which the carbon backbones of each BCAA may enter distinct degradation pathways.[7]

The oncogenic transcription factor Myc is frequently reported to drive BCAT1 expression.[8][9][10]

Clinical significance

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Two different clinical disorders have been attributed to a defect of branched-chain amino acid transamination: hypervalinemia and hyperleucine-isoleucinemia.[11] As there is also a gene encoding a mitochondrial form of this enzyme (BCAT2), mutations in either gene may contribute to these disorders.

Overexpression of BCAT1 has been associated with a variety of cancers, among them glioblastoma,[12] breast cancer,[13] acute myeloid leukemia,[14] gastric cancer[15] and chronic myeloid leukemia.[16]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000060982 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030268 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Entrez Gene: Branched chain amino acid transaminase 1". Retrieved 2016-04-21.
  6. ^ "BCAT1 - Branched-chain-amino-acid aminotransferase, cytosolic - Homo sapiens (Human) - BCAT1 gene & protein". www.uniprot.org. Retrieved 2018-08-06.
  7. ^ "BCKDH in the BCAA degradation pathway". Genome.jp. August 6, 2018. Retrieved August 6, 2018.
  8. ^ Zhou W, Feng X, Ren C, Jiang X, Liu W, Huang W, Liu Z, Li Z, Zeng L, Wang L, Zhu B, Shi J, Liu J, Zhang C, Liu Y, Yao K (June 2013). "Over-expression of BCAT1, a c-Myc target gene, induces cell proliferation, migration and invasion in nasopharyngeal carcinoma". Molecular Cancer. 12: 53. doi:10.1186/1476-4598-12-53. PMC 3698204. PMID 23758864.
  9. ^ Schuldiner O, Eden A, Ben-Yosef T, Yanuka O, Simchen G, Benvenisty N (July 1996). "ECA39, a conserved gene regulated by c-Myc in mice, is involved in G1/S cell cycle regulation in yeast". Proceedings of the National Academy of Sciences of the United States of America. 93 (14): 7143–8. Bibcode:1996PNAS...93.7143S. doi:10.1073/pnas.93.14.7143. PMC 38950. PMID 8692959.
  10. ^ Ben-Yosef T, Eden A, Benvenisty N (July 1998). "Characterization of murine BCAT genes: Bcat1, a c-Myc target, and its homolog, Bcat2". Mammalian Genome. 9 (7): 595–7. doi:10.1007/s003359900825. PMID 9657861. S2CID 21062787.
  11. ^ Wang XL, Li CJ, Xing Y, Yang YH, Jia JP (September 2015). "Hypervalinemia and hyperleucine-isoleucinemia caused by mutations in the branched-chain-amino-acid aminotransferase gene". Journal of Inherited Metabolic Disease. 38 (5): 855–61. doi:10.1007/s10545-015-9814-z. PMID 25653144. S2CID 24253640.
  12. ^ Tönjes M, Barbus S, Park YJ, Wang W, Schlotter M, Lindroth AM, et al. (July 2013). "BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wild-type IDH1". Nature Medicine. 19 (7): 901–908. doi:10.1038/nm.3217. PMC 4916649. PMID 23793099.
  13. ^ Thewes V, Simon R, Hlevnjak M, Schlotter M, Schroeter P, Schmidt K, et al. (July 2017). "The branched-chain amino acid transaminase 1 sustains growth of antiestrogen-resistant and ERα-negative breast cancer". Oncogene. 36 (29): 4124–4134. doi:10.1038/onc.2017.32. PMID 28319069. S2CID 25098058.
  14. ^ Raffel S, Falcone M, Kneisel N, Hansson J, Wang W, Lutz C, et al. (November 2017). "BCAT1 restricts αKG levels in AML stem cells leading to IDHmut-like DNA hypermethylation". Nature. 551 (7680): 384–388. Bibcode:2017Natur.551..384R. doi:10.1038/nature24294. PMID 29144447. S2CID 205261267.
  15. ^ Xu Y, Yu W, Yang T, Zhang M, Liang C, Cai X, Shao Q (May 2018). "Overexpression of BCAT1 is a prognostic marker in gastric cancer". Human Pathology. 75: 41–46. doi:10.1016/j.humpath.2018.02.003. PMID 29447920.
  16. ^ Hattori A, Tsunoda M, Konuma T, Kobayashi M, Nagy T, Glushka J, Tayyari F, McSkimming D, Kannan N, Tojo A, Edison AS, Ito T (May 2017). "Cancer progression by reprogrammed BCAA metabolism in myeloid leukaemia". Nature. 545 (7655): 500–504. Bibcode:2017Natur.545..500H. doi:10.1038/nature22314. PMC 5554449. PMID 28514443.

Further reading

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This article incorporates text from the United States National Library of Medicine, which is in the public domain.


 

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