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2 Glutaminolysis Glutaminolysis is the process by which cells convert Gln to tricarboxylic acid (TCA) cycle metabolites through the activity of multiple enzymes ( Figure 1 ) ( via SLC1A5 variant (SLC1A5_var), an AAT that locates on the mitochondrial membrane through its N-terminal targeting signal, then is decomposed into glutamate (Glu) and ammonia under the action of mitochondrial glutaminase (GLS), which is also the rate-limiting step of glutaminolysis ( via glutamate dehydrogenase 1 (GLUD1), glutamic oxaloacetic transaminase 2 (GOT2) and glutamate pyruvate transaminase 2 (GPT2) ( via SLC25A18, SLC25A22 and SLC25A11 on the mitochondrial membrane respectively ( via GOT1 ( via SLC7A11, exchanging with cystine (Cys) ( Figure 1 3 Mechanism of glutaminolysis in regulating peripheral naïve CD4 + T cell differentiation As previously mentioned, peripheral naïve CD4 + T cells can differentiate into different subtypes following antigen stimulation

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