Figure 2.
The In Silico Metabolic Model Reveals a Link between AGT LoF and Histidine Metabolism Mediated by the Action of GPT
Both AGT- and GPT-mediated reactions involve alanine, glyoxylate, glycine, and pyruvate. GPT catalyzes two different reactions in heptocytes: the non-canonical glyoxylate detoxification reaction and the canonical reversible transamination between alanine and α-ketoglutarate to generate pyruvate and glutamate. Glutamate is a key compound in amino acid degradation. Alteration of metabolic fluxes caused by AGT LoF are thus propagated via GPT to histidine metabolism. Histidine can be metabolized to glutamate and α-ketoglutarate via a step of intermediary reactions (double arrows) and/or to histamine. The conversion of histidine into histamine also occurs in other cell types.