Figure 3.

Schematic representation of metabolic pathways targeted by ODC_REMP. RNA sequencing and LC-HRMS/MS data revealed a strong impact on metabolic pathways after ODC_REMP treatment. These pathways include glycolysis, choline and ceramide metabolism. Enzymes detected to be upregulated after ODC_REMP treatment (in italics and orange), downregulated enzymes (in italic and green), and upregulated metabolites (written in red). Pyruvate can be used for the enzymatic conversion of palmitoyl-CoA, which is the primary molecule to initiate the de novo synthesis of ceramide. Molecules of the ceramide class were significantly upregulated, as well as the two enzymes ceramidase 4 and sphingomyelin phosphodiesterase 4. Pyruvate is also the substrate for pyruvate dehydrogenase phosphatase producing acetyl-CoA. This figure was created with BioRender.com. Legend: αKG, α-ketoglutarate; 1/6(bi)p, 1/6 (bis)phosphate; 3PG, 3-phosphoglyceric acid; CDP-choline, cytidine 5′-diphosphocholine; CoA, coenzyme A; DHAP, dihydroxyacetone phosphate; GA3P, glyceraldehyde 3-phosphate; GLUT, glucose transporter; MCT, monocarboxylate transporter; MPC, mitochondrial pyruvate carrier 1; NAD, nicotinamide dinucleotide; OAA, oxaloacetate; SucCoA, succinyl-CoA; TCA, citric acid cycle.