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. 2024 Jan 10;10(2):e24454. doi: 10.1016/j.heliyon.2024.e24454

Fig. 1.

Fig. 1

The metabolism of 2-HG in cancer cell. (A) The role of IDH in the TCA cycle under physiological conditions. (B) The generation of 2-HG under pathological conditions. Generally, 2-HG is transformed from its substrate α-KG. The heterogenous mutation of IDH1/2 represents the primary source of D(R)-2-HG. Additionally, PHGDH and HOT convert α-KG to D(R)-2-HG in a NADH-dependent manner. L(S)-2-HG is predominantly produced by LDHA and MDH under hypoxic conditions. Reversely, 2-HG is catabolized by 2HGDH to maintain a relatively low level. Abnormal accumulation of 2-HG promotes the tumor progression by inhibiting α-KGDDs, adapting to hypoxia and metabolism reprogramming. TCA: tricarboxylic acid; IDH: isocitrate dehydrogenase; NADP+: nicotinamide adenine dinucleotide phosphate; α-KG: α-ketoglutarate; 2-HG: 2-hydroxyglutarate; MDH: malate dehydrogenase; LDHA: lactate dehydrogenase A; 2HGDH: 2-HG dehydrogenase; HOT: hydroxyacid-oxoacid transhydrogenase; FAD: flavin adenine dinucleotide.