Chemistry:Branched chain amino acid transaminase 1

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example


Branched chain amino acid transaminase 1 is a protein that in humans is encoded by the BCAT1 gene.[1] 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.

Function

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:[2]

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.[3]

The oncogenic transcription factor Myc is frequently reported to drive BCAT1 expression.[4][5][6]

Clinical significance

Two different clinical disorders have been attributed to a defect of branched-chain amino acid transamination: hypervalinemia and hyperleucine-isoleucinemia.[7] 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,[8] breast cancer,[9] acute myeloid leukemia,[10] gastric cancer[11] and chronic myeloid leukemia.[12]

References

  1. ↑ "Entrez Gene: Branched chain amino acid transaminase 1". https://www.ncbi.nlm.nih.gov/gene/586. 
  2. ↑ "BCAT1 - Branched-chain-amino-acid aminotransferase, cytosolic - Homo sapiens (Human) - BCAT1 gene & protein" (in en). https://www.uniprot.org/uniprot/P54687. 
  3. ↑ "BCKDH in the BCAA degradation pathway". August 6, 2018. https://www.genome.jp/kegg-bin/show_pathway?ec00280+1.2.4.4. 
  4. ↑ "Over-expression of BCAT1, a c-Myc target gene, induces cell proliferation, migration and invasion in nasopharyngeal carcinoma". Molecular Cancer 12: 53. June 2013. doi:10.1186/1476-4598-12-53. PMID 23758864. 
  5. ↑ "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. July 1996. doi:10.1073/pnas.93.14.7143. PMID 8692959. Bibcode: 1996PNAS...93.7143S. 
  6. ↑ "Characterization of murine BCAT genes: Bcat1, a c-Myc target, and its homolog, Bcat2". Mammalian Genome 9 (7): 595–7. July 1998. doi:10.1007/s003359900825. PMID 9657861. 
  7. ↑ "Hypervalinemia and hyperleucine-isoleucinemia caused by mutations in the branched-chain-amino-acid aminotransferase gene". Journal of Inherited Metabolic Disease 38 (5): 855–61. September 2015. doi:10.1007/s10545-015-9814-z. PMID 25653144. 
  8. ↑ "BCAT1 promotes cell proliferation through amino acid catabolism in gliomas carrying wild-type IDH1". Nature Medicine 19 (7): 901–908. July 2013. doi:10.1038/nm.3217. PMID 23793099. 
  9. ↑ "The branched-chain amino acid transaminase 1 sustains growth of antiestrogen-resistant and ERα-negative breast cancer". Oncogene 36 (29): 4124–4134. July 2017. doi:10.1038/onc.2017.32. PMID 28319069. 
  10. ↑ "BCAT1 restricts αKG levels in AML stem cells leading to IDHmut-like DNA hypermethylation". Nature 551 (7680): 384–388. November 2017. doi:10.1038/nature24294. PMID 29144447. Bibcode: 2017Natur.551..384R. 
  11. ↑ "Overexpression of BCAT1 is a prognostic marker in gastric cancer". Human Pathology 75: 41–46. May 2018. doi:10.1016/j.humpath.2018.02.003. PMID 29447920. 
  12. ↑ "Cancer progression by reprogrammed BCAA metabolism in myeloid leukaemia". Nature 545 (7655): 500–504. May 2017. doi:10.1038/nature22314. PMID 28514443. Bibcode: 2017Natur.545..500H. 

Further reading

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



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