ScheBo^® • Tumor M2-PK^® Antibodies

The following monoclonal antibodies are available:


Tumor cells are characterized by high conversion rates of glucose to lactate - a phenomenon which was first described by Otto Warburg in 1924.

At first glance the regeneration of energy via glycolysis might seem to be a senseless waste of substrate resources. Compared to mitochondrial respiration, glycolysis consumes about 38 times more glucose to regenerate the same amount of energy.

However, glycolysis has a crucial advantage for tumor cells. In contrast to mitochondrial respiration, glycolytic energy production is independent of oxygen supply and allows tumor cells to survive and metastasize even when starved of oxygen.
But the regeneration of energy is not the only metabolic function of glycolysis in tumor cells. It is also involved in another important aspect of tumor metabolism.

A second major function of glycolysis is to provide the basic substances used to synthesize cell building blocks.

Thus, glycolytic intermediates are precursors for the synthesis of nucleic acids, amino acids and phospholipids.

In tumor cells the metabolic fate of the glucose carbons (i.e. degradation to pyruvate and lactate with production of energy, or channeling into synthetic processes) is mainly regulated by the pyruvate kinase isoenzyme type M2.

Pyruvate kinase catalyzes the final step within the glycolytic sequence - the dephosphorylation of phosphoenolpyruvate to pyruvate - and is responsible for net ATP production within this pathway.

Different isoenzymes of pyruvate kinase are expressed, dependent upon the different metabolic functions of the organs.

Tissues with high rates of gluconeogenesis, such as the liver, kidney and intestine, express the pyruvate kinase isoenzyme type L (L-PK).

Muscles and the brain, in which high amounts of energy have to be rapidly provided, are characterized by the expression of the pyruvate kinase isoenzyme type M1.

The pyruvate kinase isoenzyme type M2 (M2-PK) is expressed in some differentiated tissues, such as the lung, and is the characteristic isoenzyme of all proliferating cells, including normal proliferating cells, embryonic cells, stem cells and especially tumor cells.

During tumorigenesis a shift in the isoenzyme equipment of pyruvate kinase always takes place, such that the tissue-specific isoenzymes disappear and M2-PK is expressed.

In contrast to the other pyruvate kinase isoenzymes, which only exist in a tetrameric form, M2-PK may occur in a highly active tetrameric form but also in a nearly inactive dimeric form.

When the highly active tetrameric form of M2-PK is predominant glucose is converted to pyruvate and lactate with the production of energy, whereas the nearly inactive dimeric form of M2-PK favours the channelling of glucose carbons into synthetic processes.

In tumor cells the dimeric form of M2-PK - termed Tumor M2-PK - is mainly predominant and the amount of Tumor M2-PK correlates with the malignancy of the tumors.

This dissociation of the tetrameric form into the dimeric form in tumor cells is induced by direct interaction with various oncoproteins.

• » Protocol for immunohistology
  Immunohistochemical Staining of Pyruvate Kinase with
  the Monoclonal Antibody ScheBo^® • DF-4
  
  
• » Examples of immunohistochemical staining
  Please find here pictures of examples of immunohistochemical staining
  
  
• » Metabolic background
  Please find more detailed information about the metabolic background of L- and M2-PK under the following link:
  
  
• » References/literature
  References Tumor M2-PK Antibodies