Branched chain amino acid transaminase 1

BCAT1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	2ABJ, 2COG, 2COI, 2COJ
Identifiers
Aliases	BCAT1, BCATC, BCT1, ECA39, MECA39, PNAS121, PP18, branched chain amino acid transaminase 1
External IDs	OMIM: 113520; MGI: 104861; HomoloGene: 20320; GeneCards: BCAT1; OMA:BCAT1 - orthologs
Gene location (Human)
Chr.	Chromosome 12 (human)
End	24,949,101 bp
Gene location (Mouse)
Chr.	Chromosome 6 (mouse)
End	145,021,910 bp
RNA expression pattern
	Top expressed in
	tibia; ; synovial joint; ; retinal pigment epithelium; ; pars compacta; ; endothelial cell; ; pars reticulata; ; lateral nuclear group of thalamus; ; tendon of biceps brachii; ; lower lobe of lung; ; visceral pleura;
	Top expressed in
	cumulus cell; ; facial motor nucleus; ; otic placode; ; medulla oblongata; ; deep cerebellar nuclei; ; medial vestibular nucleus; ; dorsal tegmental nucleus; ; pontine nuclei; ; inferior colliculi; ; habenula;
	More reference expression data
	n/a
Gene ontology
Molecular function	transaminase activity; L-leucine transaminase activity; identical protein binding; catalytic activity; L-valine transaminase activity; L-isoleucine transaminase activity; transferase activity; branched-chain-amino-acid transaminase activity;
Cellular component	cytoplasm; mitochondrion; cytosol;
Biological process	metabolism; branched-chain amino acid biosynthetic process; cell population proliferation; cellular amino acid biosynthetic process; branched-chain amino acid metabolic process; leucine biosynthetic process; branched-chain amino acid catabolic process; valine biosynthetic process; G1/S transition of mitotic cell cycle;
	Sources:Amigo / QuickGO
Orthologs
	586
	12035
	ENSG00000060982
	ENSMUSG00000030268
	P54687
	P24288
	NM_001178091; NM_001178092; NM_001178093; NM_001178094; NM_005504
	NM_001024468; NM_007532
	NP_001171562; NP_001171563; NP_001171564; NP_001171565; NP_005495
	NP_001019639; NP_031558
	Wikidata
View/Edit Human	View/Edit Mouse

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.

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:^[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

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

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000060982 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000030268 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Entrez Gene: Branched chain amino acid transaminase 1". Retrieved 2016-04-21.
^ "BCAT1 - Branched-chain-amino-acid aminotransferase, cytosolic - Homo sapiens (Human) - BCAT1 gene & protein". www.uniprot.org. Retrieved 2018-08-06.
^ "BCKDH in the BCAA degradation pathway". Genome.jp. August 6, 2018. Retrieved August 6, 2018.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.

Function

Clinical significance

References

Further reading