fig1

Figure 1. Major physiological functions of α-KGDH. AKG participates in the tricarboxylic acid (TCA) cycle and serves as a key node linking carbon and nitrogen metabolism. It exerts antioxidant effects enzymatically by maintaining the oxidized/reduced nicotinamide adenine nucleotide (NAD⁺/NADH) ratio, promoting mitophagy, and enhancing the intracellular antioxidant defense system, and via non-enzymatic mechanisms by scavenging hydrogen peroxide. Its anti-inflammatory action is mediated through the modulation of macrophage polarization (M1/M2). AKG acts as an essential cofactor for 2-oxoglutarate-dependent dioxygenases (2-OGDDs), including enzymes from the ten-eleven translocation (TET) and Jumonji C (JmjC) families, thereby regulating epigenetic processes via the modulation of DNA and histone methylation. α-KGDH: α-Ketoglutarate dehydrogenase;BNIP3: BCL2/adenovirus E1B 19-kDa-interacting protein 3; FTO-m6A: fat mass and obesity associated N⁶-methyladenosine deaminase; GDH: glutamate dehydrogenase; GSH: glutathione; GSSG: glutathione disulfide; HIF-1α: hypoxia-inducible factor 1-alpha; IDH: isocitrate dehydrogenase; IL-1β: interleukin-1 beta; IL-6: interleukin-6; IL-10: interleukin-10; iNOS: inducible nitric oxide synthase; LC3B: microtubule-associated protein 1 light chain 3 beta; PINK: PTEN-induced kinase 1; ROS: reactive oxygen species; SOD: superoxide dismutase; STAT3: signal transducer and activator of transcription 3; TNF-α: tumor necrosis factor alpha; 5mC: 5-methylcytosine.