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This convergence of genetic and pharmacological perturbations supports a model in which ADORA2b ablation shifts RBC metabolism toward the PPP, while caffeine imposes a dual inhibitory effect – blocking both ADORA2b signaling and G6PD enzymatic activity – ultimately compounding the impairment of RBC energy and redox homeostasis

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Mitochondrial oxidation of fatty acids generates acetyl-CoA which can be further oxidized in the TCA cycle