Fig. 1 |. KRAS* rewires cancer cell metabolism.

a | Glucose (Glc) transport via glucose transporters (GLUTs) and flux through glycolysis is upregulated to provide intermediates for branching biosynthetic pathways. The hexosamine biosynthetic pathway (HBP) produces uridine diphosphate N-acetylglucosamine (UDP-GlcNAc) for glycosylation. The two arms of the pentose phosphate pathway (PPP) generate nicotinamide adenine dinucleotide phosphate (NADPH) as well as ribose bases for nucleotide synthesis. Flux through the serine biosynthesis pathway (SBP) generates the amino acids serine (Ser) and glycine (Gly). To maintain redox balance, increased expression of lactate dehydrogenase (LDH) converts pyruvate (Pyr) to lactate (Lac), which is transported out of the cell via monocarboxylate transporters (MCTs) to sustain glycolysis. Pyruvate also contributes carbon to the tricarboxylic acid (TCA) cycle in mitochondria. Glutamine (Gln) is imported by SLC1A5 and converted to glutamate (Glu) by glutaminase 1 (GLS1) and fuels the TCA cycle. Mutant KRAS (KRAS*) diverts TCA cycle intermediates through malic enzyme 1 (ME1) for NADPH production, as well as synthesis of amino acids such as aspartate (Asp) and asparagine (Asn). b | KRAS* cells are dependent on nutrient-scavenging pathways, such as macropinocytosis and autophagy, whereby free biosynthetic precursors are released for utilization by cancer cells. c | KRAS* regulates mitochondrial dynamics through DRP1 to fine-tune mitochondrial fission and maintain optimal reactive oxygen species (ROS) levels for signalling, while avoiding toxicity. d | Depending on the intracellular redox state, KRAS* cells use fatty acid synthesis (FAS) to regenerate NAD(P)⁺ and synthesize lipids or fatty acid oxidation (FAO), whereby lipids are used for energy and NAD(P)H production. AA, amino acid; FA, fatty acid; Fe²⁺, iron.