Figure 3.

Metabolism in HCV infected cells. The major metabolic pathways that use glucose (Glc) to either drive nucleotide synthesis and NADPH production via the pentose phosphate shunt (PPP) or to drive the TCA cycle and respiration in mitochondria are depicted. TCA reactions catalyze the reduction of NAD⁺ and FAD into NADH and FADH₂, which in turn feed the electron transport chain (ETC). The ETC maintains the mitochondrial membrane potential, mtΔΨ, required for ATP synthesis. Electrons that leak from complex I and IV of the ETC form reactive oxygen species (ROS). ROS scavenging requires reduced glutathione (GSH), which is oxidized in the process. Recycling of the GSH pool requires NADPH, which is mainly produced by the PP shunt. Glucose-6-phosphate (G6P), pyruvate (Pyr), lactate (Lac), acetyl coenzyme A (AcCoA), pyruvate dehydrogenase complex (PDC), citrate synthase (CS), aconitase (ACO), isocitrate dehydrogenase (ICDH), α-ketoglutarate dehydrogenase (αKGDH), succinyl coenzyme A ligase (SuCLA), succinate dehydrogenase (SDH), fumarate hydratase (FH), malate dehydrogenase (MDH). Factors and events targeted by HCV are indicated by red stars and include: activation of glycolytic enzymes (1) with potential re-routing of the flux into the pentose phosphate shunt, (2) induction of TCA cycle (3) and lipogenic enzymes (4) and complex I of the ETC (5).