| Product Includes | Product # | Quantity | Mol. Wt | Isotype/Source |
|---|---|---|---|---|
| Phospho-Pyruvate Dehydrogenase α1 (Ser293) (E4V9L) Rabbit mAb | 37115 | 20 µl | 43 kDa | Rabbit IgG |
| Pyruvate Dehydrogenase (C54G1) Rabbit mAb | 3205 | 20 µl | 43 kDa | Rabbit IgG |
| PDHK1 (C47H1) Rabbit mAb | 3820 | 20 µl | 47 kDa | Rabbit IgG |
| LDHA (C4B5) Rabbit mAb | 3582 | 20 µl | 37 kDa | Rabbit IgG |
| LDHB (E8J8T) Rabbit mAb | 56298 | 20 µl | 37 kDa | Rabbit IgG |
| Anti-rabbit IgG, HRP-linked Antibody | 7074 | 100 µl | Goat |
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Description
The Glycolysis/TCA Cycle Molecular Checkpoint Antibody Sampler Kit provides an economical means of detecting select components involved in the regulation of the connection between glycolysis and the citric acid cycle (tricarboxylic acid (TCA) cycle). The kit includes enough antibodies to perform two western blot experiments with each primary antibody.
Storage
Background
The pyruvate dehydrogenase complex catalyzes the conversion of pyruvate and CoA into acetyl-CoA and CO2 in the presence of NAD+. Acetyl-CoA then goes into the citric acid cycle (tricarboxylic acid (TCA) cycle), where it reacts with oxaloacetate to form citrate. The reaction of oxidative decarboxylation of pyruvate serves as a critical link between glycolysis and the citric acid cycle (TCA cycle). In mammalian cells, the pyruvate dehydrogenase complex is located in the mitochondrial matrix (1). This complex is composed of three enzymes: pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (E2), and dihydrolipoamide dehydrogenase (E3). Pyruvate dehydrogenase (E1) consists of two subunits: α and β. This enzyme catalyzes the removal of CO2 from pyruvate. Mutations in the α subunits of pyruvate dehydrogenase (E1) lead to congenital defects that are usually associated with lactic acidosis, neurodegeneration, and early death (2).
Pyruvate dehydrogenase kinase 1 (PDHK1) phosphorylates pyruvate dehydrogenase (E1) α1 subunit at Ser293 to inactivate its activity (3,4). This phosphorylation contributes to the tumor metabolic reprogramming toward glycolysis in hypoxia by inhibiting the citric acid cycle (TCA cycle) (4).
Lactate dehydrogenase (LDH) catalyzes the reversible conversion between pyruvate and lactate. LDH is a tetramer composed of various combinations of LDHA subunit and LDHB subunit to form five different isozymes. LDHA has a higher affinity for pyruvate and preferentially catalyzes the conversion of pyruvate to lactate. LDHA levels are upregulated in many cancers. On the other hand, LDHB has a higher affinity for lactate and preferentially catalyzes the conversion of lactate to pyruvate, enabling cells to use lactate as a nutrient (5-7). Studies show that LDHA/LDHB deficiency suppresses glycolysis and ATP production, inhibiting STING signaling and antitumor immune responses mediated by dendritic cells (8). In addition, acetylation of LDHB inhibits its activity, reduces hepatic lactate clearance, and promotes the progression of non-alcoholic fatty liver disease (NAFLD) (9).
- Strumiło, S. (2005) Acta Biochim Pol 52, 759-64.
- Stacpoole, P.W. et al. (2003) Curr Gene Ther 3, 239-45.
- Fan, J. et al. (2014) J Biol Chem 289, 26533-26541.
- Chae, Y.C. et al. (2016) Cancer Cell 30, 257-272.
- Doherty, J.R. and Cleveland, J.L. (2013) J Clin Invest 123, 3685-92.
- Hong, S.M. et al. (2019) J Biol Chem 294, 7810-7820.
- Urbańska, K. and Orzechowski, A. (2019) Int J Mol Sci 20, 2085. doi: 10.3390/ijms20092085.
- Hu, Z. et al. (2023) J Clin Invest 133, e166031. doi: 10.1172/JCI166031.
- Wang, T. et al. (2021) J Hepatol 74, 1038-1052.
Background References
Trademarks and Patents
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