Sandwich ELISA s based on two monoclonal antibodies which specifically recognize Tumor M2-PK ( the dimeric form of M2-PK ) are available for the quantification of Tumor M2-PK in stool and EDTA-plasma samples respectively.
22.
Oxygen starvation or highly accumulated glycolytic intermediates, such as fructose 1, 6-bisphosphate ( fructose 1, 6-P2 ) or the amino acid serine, induce the reassociation of the dimeric form of M2-PK to the tetrameric form.
23.
Due to the key position of pyruvate kinase within glycolysis, the tetramer : dimer ratio of PKM2 determines whether glucose carbons are converted to pyruvate and lactate under the production of energy ( tetrameric form ) or channelled into synthetic processes ( dimeric form ).
24.
In tumor cells, PKM2 is mainly in the dimeric form and has, therefore, been termed Tumor M2-PK . The quantification of Tumor M2-PK in plasma and stool is a tool for early detection of tumors and follow-up studies during therapy.
25.
When PKM2 is mainly in the less active dimeric form, which is the case in tumor cells, all glycolytic intermediates above pyruvate kinase accumulate and are channelled into synthetic processes, which branch off from glycolytic intermediates such as nucleic acid-, phospholipid-, and amino acid synthesis.
26.
Consequently, due to the activation of M2-PK, glucose is converted to pyruvate and lactate under the production of energy until the fructose 1, 6-P2 levels drop below a certain threshold value, which allows the dissociation of the tetrameric form of M2-PK to the dimeric form.
27.
When M2-PK is mainly in the dimeric form, which is the case in tumor cells, all phosphometabolites above pyruvate kinase accumulate and are channelled into synthetic processes which branch off from glycolytic intermediates, such as nucleic acids, phospholipids and amino acids, important cell building blocks for highly proliferating cells such as tumor cells.
28.
This gene encodes a monomeric protein which shares a 70 % amino acid sequence identity, as well as conserved chain folds and flavin adenine dinucleotide ( FAD )-binding site structures, with MAO-B . However, MAO-A has a monopartite cavity of approximately 550 angstroms, compared to the 290-angstrom bipartite cavity in MAO-B . Nonetheless, both proteins adopt dimeric forms when membrane-bound.
29.
The tetrameric form is the pyruvate kinase structure in its R-state conformation, namely with high binding affinity to PEP . In contrast, the dimeric form is its structure in T-state conformation, namely with a low binding affinity to PEP . As a result, gene expression can be regulated by converting the highly active tetrameric form of PKM2, which yields high PEP concentrations, into an inactive dimeric form, which yields a PEP concentration of nearly zero.
30.
The tetrameric form is the pyruvate kinase structure in its R-state conformation, namely with high binding affinity to PEP . In contrast, the dimeric form is its structure in T-state conformation, namely with a low binding affinity to PEP . As a result, gene expression can be regulated by converting the highly active tetrameric form of PKM2, which yields high PEP concentrations, into an inactive dimeric form, which yields a PEP concentration of nearly zero.
