Fig. 1

Overview of the most important metabolic processes to generate energy in human cells: glycolysis, mitochondrial respiration, glutaminolysis and fatty acid oxidation. (1) During glycolysis, glucose is taken up into the cells by glucose transporters (GLUT) and converted into pyruvate by several enzymatic processes. Finally, pyruvate is transformed into lactate, which is transported out of the cell by monocarboxylate transporters (MCT). Pyruvate can also be converted to acetyl-CoA by pyruvate dehydrogenase kinase (PDK), which then enters the tricarboxylic acid (TCA) cycle for mitochondrial respiration (2). During this multistep process, NADH and FADH₂ are produced. Both molecules are necessary to complete the oxidative phosphorylation and drive the electron transport chain, resulting in the production of ATP. 3) During glutaminolysis, glutamine is taken up into the cells by several soluble carrier (SLC) transporters including large amino acid transporter 1 (LAT1, also known as SLC7A5), alanine, serine, cysteine transporter 2 (ASCT2 also known as SLC1A5) and sodium-coupled neutral acid transporter 1 (SNAT1 also known as SLC38A1). Once glutamine is intracellularly present, glutamine is transformed into glutamine and α-ketoglutarate, where it enters the TCA cycle. 4) Finally, fatty acids are taken up into the cell by fatty acid binding protein (FABP), fatty acid transporter protein (FATP) and CD63/fatty acid translocase, where fatty acids are converted into long chain fatty acids and acyl-carnithine, followed by translocation to the inner mitochondrial membrane, where acyl-carnithine is transformed into acyl-CoA and carnithine. During β-oxidation, acyl-CoA undergoes several reactions, generating NADH, FADH₂ (both necessary for the electron transport chain during oxidative phosphorylation) and acyl-CoA and acetyl-CoA (necessary for TCA cycle). Enzymes are shown in grey. HK: hexokinase, PGI: phosphoglucose isomerase, PFK: phosphofructokinase, GAPDH: glyceraldehyde-3-phosphate dehydrogenase, PGK: phosphoglycerate kinase, PGM: phosphoglyceromutase, PK: pyruvate kinase, LDH: lactate dehydrogenase, ACLY: ATP citrate lyase, ACC: acetyl-CoA carboxylase, PDK: pyruvate dehydrogenase kinase, AA: amino acid, GLS: glutaminase, GDH: glutamate dehydrogenase, FAS: fatty acid synthase, FA: fatty acid, ADP: adenosine diphosphate, ATP: adenosine triphosphate, NAD: nicotinamide adenine dinucleotide, FAD: flavin adenine dinucleotide, PPP: pentose phosphate pathway, GDP: guanine diphosphate, GTP: guanine triphosphate, Cyt C: cytochrome C, CoQ: coenzyme Q₁₀. Created with BioRender.com