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-Glutamate(2-Oxoglutarate) Aminotransferases
Published in Elling Kvamme, Glutamine and Glutamate in Mammals, 1988
Pardridge and Davidson118 reemphasize Krebs’ earlier suggestion that alanine formation by skeletal muscle is driven by the tendency to establish equilibrium between linked aminotransferases.119 For example, Krebs, in discussing the ALAAT and ASPAT reactions showed that at equilibrium, the alanine concentration in resting rat muscle should be 3 to 4 mM but is, in fact, 1.5 mM. This means that the components of the linked aminotransferases are not in thermodynamic equilibrium and alanine is “shed” into the blood because of the much lower concentration of alanine in the blood. In addition to ALAAT and ASPAT, the skeletal muscle contains branched-chain amino acid aminotransferase (BCAAT) activity; stimulation of alanine production by, for example, branched-chain amino acids could conceivably result in net alanine formation via a readjustment of the reactions of aminotransferases toward a new equilibrium. Pardridge and Davidson118 suggest that alanine production is linked to pyruvate “overflow”. That is, the rate of pyruvate production from glucose or from gluconeogenic amino acids must exceed the demand for pyruvate consumption via mitochondrial oxidation before net alanine production will occur.
Reduced branched-chain aminotransferase activity alleviates metabolic vulnerability caused by dim light exposure at night in Drosophila
Published in Journal of Neurogenetics, 2023
Mari Kim, Gwang-Ic Son, Yun-Ho Cho, Gye-Hyeong Kim, Sung-Eun Yoon, Young-Joon Kim, Jongkyeong Chung, Eunil Lee, Joong-Jean Park
Branched-chain amino acids (BCAAs), including leucine (Leu), isoleucine (Ile), and valine (Val), are essential amino acids. In cells, BCAAs are transaminated by branched-chain amino acid aminotransferase (BCAT) and decarboxylated by branched-chain α-keto acid dehydrogenase enzyme complex (BCKDC). BCAAs are finally converted to acetyl-CoA or succinyl-CoA to generate ATP in the tricarboxylic acid (TCA) cycle (Nie et al., 2018). Feeding BCAAs to middle-aged mice increases mitochondrial biosynthesis in cardiac and skeletal muscles. It improves the healthy lifespan by activating the mammalian target of rapamycin (mTOR) and sirtuin 1 (SIRT1) signaling and reactive oxygen species (ROS) defense systems, such as superoxide dismutase 1 (SOD1) and glutathione peroxidase 1 (GPx1) (D’Antona et al., 2010). In addition, BCAAs are effectively metabolized in immune cells and play a role in immune cell growth, proliferation, and activation (Monirujjaman & Ferdouse, 2014). However, side effects occur when excess BCAAs are accumulated. For example, maple syrup urine disease (MSUD) can develop when BCAA levels in the blood are abnormally high due to decreased activity of BCKDC. Patients with MSUD are more sensitive to oxidative stress and have impaired brain function, showing increased levels of BCAAs, ketonic acids, and free radicals in the blood (Sitta et al., 2014; Strauss et al., 2020). The suppression of BCAT activity by overexpressing miR-277 in Drosophila leads to mTOR activation, BCAA accumulation, and a shortened lifespan (Esslinger et al., 2013).