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Primary Roles of Branched Chain Amino Acids (BCAAs) and Their Metabolism in Physiology and Metabolic Disorders.
Molecules
December 2024
Department of Biochemistry and Molecular Biology, Graduate School of Medical Science, Yamagata University, Yamagata 990-9585, Japan.
Leucine, isoleucine, and valine are collectively known as branched chain amino acids (BCAAs) and are often discussed in the same physiological and pathological situations. The two consecutive initial reactions of BCAA catabolism are catalyzed by the common enzymes referred to as branched chain aminotransferase (BCAT) and branched chain α-keto acid dehydrogenase (BCKDH). BCAT transfers the amino group of BCAAs to 2-ketoglutarate, which results in corresponding branched chain 2-keto acids (BCKAs) and glutamate.
View Article and Find Full Text PDFBCAT1 Associates with DNA Repair Proteins KU70 and KU80 and Contributes to Regulate DNA Repair in T-Cell Acute Lymphoblastic Leukemia (T-ALL).
Int J Mol Sci
December 2024
Immunology and Molecular Oncology Diagnostics, Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy.
Increased expression of branched-chain amino acid (BCAA) transaminase 1 (BCAT1) often correlates with tumor aggressiveness and drug resistance in cancer. We have recently reported that BCAT1 was overexpressed in a subgroup of T-cell acute lymphoblastic (T-ALL) samples, especially those with NOTCH1 activating mutations. Interestingly, BCAT1-depleted cells showed pronounced sensitivity to DNA-damaging agents such as etoposide; however, how BCAT1 regulates this sensitivity remains uncertain.
View Article and Find Full Text PDFGut microbiota-mediated hsa_circ_0126925 targets BCAA metabolic enzyme BCAT2 to exacerbate colorectal cancer progression.
Mol Cancer Res
December 2024
First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China.
Recent evidence indicates that a high-fat diet (HFD) can promote tumor development, especially colorectal cancer (CRC), by influencing the microbiota. Regulatory circular RNAs (circRNAs) play an important role in modulating host-microbe interactions; however, the specific mechanisms by which circRNAs influence cancer progression by regulating these interactions remain unclear. Here, we report that consumption of a HFD modulates the microbiota by specifically upregulating the expression of the noncoding RNA hsa_circ_0126925 (herein referred to as circ_0126925) in CRC.
View Article and Find Full Text PDFBranched-chain amino acid catabolism promotes M2 macrophage polarization.
Front Immunol
November 2024
Shanghai Key Laboratory of Metabolic Remodeling and Health, Institute of Metabolism and Integrative Biology, Fudan University, Shanghai, China.
Introduction: During an immune response, macrophages undergo systematic metabolic rewiring tailored to support their functions. Branched-chain amino acid (BCAA) metabolism has been reported to modulate macrophage function; however, its role in macrophage alternative activation remain unclear. We aimed to investigate the role of BCAA metabolism in macrophage alternative activation.
View Article and Find Full Text PDFResearch advances in branched-chain amino acid metabolism in tumors.
Mol Cell Biochem
November 2024
The Affiliated Wuxi No. 2 Hospital of Nanjing Medical University, Wuxi, China.
The metabolic reprogramming of amino acids is an important component of tumor metabolism. Branched-chain amino acids (BCAAs) perform important functions in tumor progression. They are the important amino donor and are involved in the synthesis of various non-essential amino acids, nucleotides, and polyamines to satisfy the increased demand for nitrogen sources.
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