Journal of Cancer Prevention

eISSN 2288-3657
pISSN 2288-3649
Fig. 3.

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Fig. 3. A model of BCAA metabolism in tumor manifestation. Cancer cells are likely to obtain BCAAs from the tumor microenvironment or protein degradation as essential amino acids. BCAAs play distinct roles in cancer cells. Thus, BCAAs can activate the mTORC1 signalling, which stimulates protein translation, growth, and survival. They also serve as building blocks in protein synthesis and can be metabolized into BCKAs in the cytosol by BCAT1 and/or mitochondria by BCAT2, a process involving the conversion of α-KG to glutamate. BCAAs are also used as indirect nitrogen sources for nucleotide and non-essential amino acid biosynthesis via the glutamate-glutamine axis, and further catabolized to yield acetyl-CoA and succinyl-CoA that feed into the TCA cycle, thereby contributing to energy production. The acetyl-CoA levels have an impact on the epigenetic changes of cells. It can influence diverse cellular processes, such as gene expression, cell-cycle progression and DNA repair. In some cancers such as chronic myeloid leukemia, BCAT1 is thought to convert BCKAs back to BCAAs. mTORC1, mTOR complex 1; BCAAs, branched-chain amino acids; BCAT, branched-chain aminotransferase; α-KG, α-ketoglutarate; BCKAs, branched-chain α-keto acids; TCA, tricarboxylic acid; BCKDH, branched-chain α-keto acid dehydrogenase; R-CoAs, branched-chain acyl-CoAs.
J Cancer Prev 2021;26:237~243
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