Transaminaza 1 razgranatih aminokiselinskih lanaca je protein-enzim koji je kod ljudi kodiran genom BCAT1.[5] To je prvi enzim na putu razgradnje aminokiselina razgranatog lanca (BCAA) i olakšava reverzibilnu transaminaciju BCAA i glutamata. BCAT1 se nalazi u citoplazmi, dok se njegova izoforma, BCAT2 nalazi u mitohondrijama.

BCAT1
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

2ABJ, 2COG, 2COI, 2COJ

Identifikatori
AliasiBCAT1
Vanjski ID-jeviOMIM: 113520 MGI: 104861 HomoloGene: 20320 GeneCards: BCAT1
Lokacija gena (čovjek)
Hromosom 12 (čovjek)
Hrom.Hromosom 12 (čovjek)[1]
Hromosom 12 (čovjek)
Genomska lokacija za BCAT1
Genomska lokacija za BCAT1
Bend12p12.1Početak24,810,024 bp[1]
Kraj24,949,101 bp[1]
Lokacija gena (miš)
Hromosom 6 (miš)
Hrom.Hromosom 6 (miš)[2]
Hromosom 6 (miš)
Genomska lokacija za BCAT1
Genomska lokacija za BCAT1
Bend6 G3|6 77.27 cMPočetak144,939,561 bp[2]
Kraj145,021,910 bp[2]
Ontologija gena
Molekularna funkcija transaminase activity
L-leucine transaminase activity
vezivanje identičnih proteina
catalytic activity
L-valine transaminase activity
L-isoleucine transaminase activity
aktivnost sa transferazom
branched-chain-amino-acid transaminase activity
Ćelijska komponenta citoplazma
mitohondrija
citosol
Biološki proces metabolizam
branched-chain amino acid biosynthetic process
Ćelijska proliferacija
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
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_001178091
NM_001178092
NM_001178093
NM_001178094
NM_005504

NM_001024468
NM_007532

RefSeq (bjelančevina)

NP_001171562
NP_001171563
NP_001171564
NP_001171565
NP_005495

NP_001019639
NP_031558

Lokacija (UCSC)Chr 12: 24.81 – 24.95 MbChr 6: 144.94 – 145.02 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Aminokiselinska sekvenca

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Dužina polipeptidnog lanca je 386 aminokiselina, a molekulska težina 42.966 Da.[6].

1020304050
MKDCSNGCSAECTGEGGSKEVVGTFKAKDLIVTPATILKEKPDPNNLVFG
TVFTDHMLTVEWSSEFGWEKPHIKPLQNLSLHPGSSALHYAVELFEGLKA
FRGVDNKIRLFQPNLNMDRMYRSAVRATLPVFDKEELLECIQQLVKLDQE
WVPYSTSASLYIRPTFIGTEPSLGVKKPTKALLFVLLSPVGPYFSSGTFN
PVSLWANPKYVRAWKGGTGDCKMGGNYGSSLFAQCEAVDNGCQQVLWLYG
EDHQITEVGTMNLFLYWINEDGEEELATPPLDGIILPGVTRRCILDLAHQ
WGEFKVSERYLTMDDLTTALEGNRVREMFGSGTACVVCPVSDILYKGETI
HIPTMENGPKLASRILSKLTDIQYGREESDWTIVLS

Funkcija

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Ovaj gen kodira citosolni oblik enzim transaminaze aminokiselina razgranatog lanca. Ovaj enzim katalizira reverzibilne transaminacije alfa-keto kiselina razgranatog lanca (BCKA) u aminokiseline razgranatog lanca (BCAA) valin, leucin i izoleucin , koji su neophodni za rast ćelija. Kod ljudi, njegova primarna uloga je deaminacija BCAA, jer im nedostaju enzimi za sintezu BCKA de novo. Odgovarajući kofaktori su alfa-ketoglutarat i glutamat. Odgovarajuće reakcije su:

L-leucin + 2-oksoglutarat = 4-metil-2-oksopentanoat + L-glutamat
L-izoleucin + 2-oksoglutarat = (S)-3-metil-2-oksopentanoat + L-glutamat
L-valin + 2-oksoglutarat = 3-metil-2-oksobutanoat + L-glutamat[7]

Ćelije mogu dalje razgraditi BCKA pomoću kompleksa dehidrogenaze keto-kiseline s razgranatim lancem iz kojeg ugljikove okosnice svakog BCAA mogu ući u različite puteve razgradnje.[8]

Često se izvještava da onkogeni transkripcijski faktor Myc podstiče ekspresiju BCAT1.[9][10][11]

Klinički značaj

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Dva različita klinička poremećaja pripisana su defektu transaminacije aminokiselina razgranatog lanca: hipervalinemija i hiperleucin-izoleucinemija.[12] Budući da postoji i gen koji kodira mitohondrijski oblik ovog enzima (BCAT2), mutacije oba gena mogu pridonijeti ovim poremećajima.

Prekomjerna ekspresija BCAT1 povezana je s različitim tipovima karcinoma, među njima glioblastomom,[13] rakom dojke,[14] akutnom mijeloidnom leukemijom,[15] rakom želuca[16] i hroničnom mijeloidnom leukemijom.[17]

Reference

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000060982 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030268 - Ensembl, maj 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". Pristupljeno 21. 4. 2016.
  6. ^ "UniProt, P54687". Pristupljeno 7. 8. 2021.
  7. ^ "BCAT1 - Branched-chain-amino-acid aminotransferase, cytosolic - Homo sapiens (Human) - BCAT1 gene & protein". www.uniprot.org (jezik: engleski). Pristupljeno 6. 8. 2018.
  8. ^ "BCKDH in the BCAA degradation pathway". Genome.jp. 6. 8. 2018. Pristupljeno 6. 8. 2018.
  9. ^ 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 (juni 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.
  10. ^ Schuldiner O, Eden A, Ben-Yosef T, Yanuka O, Simchen G, Benvenisty N (juli 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.
  11. ^ Ben-Yosef T, Eden A, Benvenisty N (juli 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.
  12. ^ Wang XL, Li CJ, Xing Y, Yang YH, Jia JP (septembar 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.
  13. ^ Tönjes M, Barbus S, Park YJ, Wang W, Schlotter M, Lindroth AM, et al. (juli 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.
  14. ^ Thewes V, Simon R, Hlevnjak M, Schlotter M, Schroeter P, Schmidt K, et al. (juli 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.
  15. ^ Raffel S, Falcone M, Kneisel N, Hansson J, Wang W, Lutz C, et al. (novembar 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.
  16. ^ Xu Y, Yu W, Yang T, Zhang M, Liang C, Cai X, Shao Q (maj 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.
  17. ^ Hattori A, Tsunoda M, Konuma T, Kobayashi M, Nagy T, Glushka J, Tayyari F, McSkimming D, Kannan N, Tojo A, Edison AS, Ito T (maj 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.

Dopunska literatura

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