PKM2: metabolic consequences of the dimeric form


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Explanation:

When M2-PK (PKM2) is in the less active dimeric form all phosphometabolites above pyruvate kinase such as glycerate 3-P and fructose 1,6-P2 accumulate and are then available as precursors for synthetic processes such as nucleic acid, phospholipid and amino acid synthesis.

Consequently:  

  • ADP and GDP levels are high
    (= substrates of PK).
  • ATP and GTP levels are low
    (= products of the PK reaction).
  • Phosphometabolite levels are high.
  • Product levels of synthetic processes, such as UTP and CTP are high.
  • (ATP+GTP) : (UTP+CTP) ratio is low.
  • Energy is provided by glutaminolysis.
  • When the fructose 1,6-P2 levels reach a certain high value the dimeric form of M2-PK (PKM2) reassociates to the tetrameric form. Then glucose is converted to lactate until the fructose 1,6-P2 levels drop below a minimum signal level. As a consequence M2-PK (PKM2) dissociates to the dimeric form and this oscillating cycle starts again.