Fig. 1 | Scientific Reports

Fig. 1

From: Metabolomic reprogramming of the tumor microenvironment by dual arginase inhibitor OATD-02 boosts anticancer immunity

Fig. 1

Modulation of L-arginine metabolism by the arginase inhibitor OATD-02 in cytosolic and mitochondrial compartments. OATD-02 inhibits arginase 1 (ARG1) in the cytosol and arginase 2 (ARG2) in mitochondria, altering key metabolic pathways. ARG1 inhibition prevents L-arginine catabolism into L-ornithine and urea, thereby reducing polyamine synthesis (putrescine, spermidine, and spermine) catalyzed by L-ornithine decarboxylase (ODC), spermidine synthase (SRM), and spermine synthase (SMS), which may limit tumor cell proliferation. ARG2 inhibition restricts L-ornithine availability in mitochondria, reducing proline biosynthesis via L-ornithine aminotransferase (OAT) and the pyrroline-5-carboxylate (P5C) pathway, which involves P5C synthase (P5CS), P5C dehydrogenase (PDG), and P5C reductase (P5CR). This metabolic shift may impair tumor adaptation to hypoxia and metabolic stress. The dual inhibition of ARG1 and ARG2 by OATD-02 may enhance antitumor effects by modulating polyamine metabolism, amino acid availability, and redox homeostasis.

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