Glycolytic and mitochondrial metabolic enzymes (None)

Glycolytic and mitochondrial metabolic enzymes represent a broad collective of proteins responsible for cellular energy production and the generation of biosynthetic precursors. Glycolytic enzymes, such as hexokinase and phosphofructokinase, facilitate the anaerobic breakdown of glucose in the cytosol, a process frequently upregulated in cancer cells to support rapid proliferation, known as the Warburg effect [1]. Mitochondrial enzymes, including those within the tricarboxylic acid (TCA) cycle and the electron transport chain (ETC), drive oxidative phosphorylation to produce the majority of cellular ATP under aerobic conditions [2]. Dysregulation of these pathways is a hallmark of various diseases; for instance, mutations in mitochondrial enzymes like isocitrate dehydrogenase (IDH) are oncogenic drivers in leukemia and glioma [3]. Therapeutic strategies target these enzymes to disrupt the metabolic advantages of diseased cells, such as using metformin to inhibit Complex I of the ETC or small molecule inhibitors for mutant IDH1/2 [4]. However, because these enzymes are fundamental to the survival of all healthy cells, targeting them requires high specificity to avoid systemic toxicity in high-energy-demand organs like the brain and heart [5]. (Citations: [1] Lunt & Vander Heiden, Annu Rev Cell Dev Biol, 2011; [2] Spinelli & Haigis, Nat Cell Biol, 2018; [3] Liberti & Locasale, Trends Biochem Sci, 2016; [4] Rena et al., Diabetologia, 2017; [5] Weinberg & Chandel, Nat Chem Biol, 2015).

Other names

Metabolic enzymesCentral carbon metabolism enzymesGlycolysis and oxidative phosphorylation enzymesEnergy metabolism enzymes

Inhibition of specific enzymatic steps to disrupt ATP production, reduce the availability of biosynthetic precursors, or reverse metabolic reprogramming in pathological cells.