Tricarboxylic Acid Cycle Antibody Sampler Kit

Background

The tricarboxylic acid (TCA) cycle includes various enzymatic reactions that constitute a key part of cellular aerobic respiration. The transport of the glycolytic end product pyruvate into mitochondria and the decarboxylation of pyruvate in the TCA cycle generate energy through oxidative phosphorylation under aerobic conditions (1,2). Two inner mitochondrial membrane proteins, mitochondrial pyruvate carrier 1 (MPC1) and mitochondrial pyruvate carrier 2 (MPC2), form a 150 kDa complex and are essential proteins in the facilitated transport of pyruvate into mitochondria (1,2). Citrate synthase catalyzes the first and rate-limiting reaction of the TCA cycle (3). Mitochondrial aconitase 2 (ACO2) catalyzes the conversion of citrate to isocitrate via cis-aconitate (4). IDH1 and IDH2 are two of the three isocitrate dehydrogenases that catalyze oxidative decarboxylation of isocitrate to α-ketoglutarate (α-KG) (5). IDH1 functions as a tumor suppressor in the cytoplasm and peroxisomes, whereas IDH2 is in mitochondria and is involved in the TCA cycle (5). Mutations in IDH2 have also been identified in malignant gliomas (6). Dihydrolipoamide succinyltransferase (DLST) is a subunit of the α-ketoglutarate dehydrogenase complex, a key enzymatic complex in the TCA cycle (7). Succinate dehydrogenase subunit A (SDHA) is a component of the TCA cycle and the electron transport chain and is involved in the oxidation of succinate (8). Fumarase catalyzes the conversion of fumarate to malate (9). Fumarase deficiency leads to the accumulation of fumarate, an oncometabolite that has been shown to promote epithelial-to-mesenchymal-transition (EMT), a developmental process that has been implicated in oncogenesis (10).