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4.3 Glutamine Glutamine (Gln) is mainly converted through GLS/glutamate dehydrogenase (GLUD)-related reactions to generate α-KG, which enters the TCA cycle and provides anaplerotic substrates for oxidative metabolism, while also influencing polarization-related epigenetic regulatory processes through metabolic ratios such as α-KG/succinate (26, Glutamine (Gln) metabolism in macrophage polarization is mainly manifested as a composite regulatory axis of “TCA cycle anaplerosis-mitochondrial metabolism-epigenetic coupling.” Its role is usually not reflected by the output of a single effector molecule, but rather by the coordinated shaping of polarization-related transcriptional programs through metabolic flux and key intermediates, particularly α-KG (26, α-KG is considered a key hub linking Gln metabolism to phenotypic remodeling (26)
