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Pyruvate Kinase Isozymes to treat Cancer

Pyruvate Kinase Isozymes to treat Cancer. Joe DeCarolis. Pyruvate Kinase Isozymes. What are Isozymes ? : Isozymes are similar enzymes that catalyze the same reactions but differ in amino acid sequences. The types of PK Isozymes in Humans are M1 and M2

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Pyruvate Kinase Isozymes to treat Cancer

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  1. Pyruvate Kinase Isozymes to treat Cancer Joe DeCarolis

  2. Pyruvate Kinase Isozymes • What are Isozymes? : Isozymes are similar enzymes that catalyze the same reactions but differ in amino acid sequences. • The types of PK Isozymes in Humans are M1 and M2 • Both are used in the degradation of glucose

  3. Difference Between PKM1 and PKM2 • M1 are converted from M2 cells and are present in skeletal muscle, heart muscle and the brain during development. When M1 is subjected to Carcinogenisisit reverses the conversion back to M2 Enzymes. PKM1 catalyzes the production of pyruvatebetter and more efficeintlythan PKM2. • M2 is solely present in embryonic tissues and are specifically expressed in proliferating cells, such as embryonic stem cells, embryonic carcinoma cells as well as cancer cells. They are replaced by other enzymes as the cells become differentiated. When phosphorilated with phosphotyrosine peptides it converts the enzyme from the tetrameric to dimericform which transforms it into a transcriptional coactivatorwhich has been located in the nucleus of cancer cells.

  4. Aerobic and Anaerobic • In carbohydrate metabolism cancer cells rely on anaerobic metabolism whereas normal cells tend to utilize aerobic degradation of glucose to obtain energy. • By doing this the cancer cells used the energy to replicate itself instead of making energy for the body and it’s processes.

  5. Different Processes

  6. Can PKM2 Be Reglated? • Specifically the NIH set out to activate the PKM2 isozyme to in hope of switching the metabolism of cancer cells (anaerobic) to that of normal cells (aerobic). • They found that using metabolic intermediates, such as fructose 1,6-P2, several amino acids and fatty acids they could convert the metabolism which stopped the cancer from growing.

  7. Some Results

  8. Sources: • Cancer MetabolismCell, Volume 148, Issue 3, 3 February 2012, Pages 383,385 • Pyruvatekinase type M2: A key regulator of the metabolic budget system in tumor cellsThe International Journal of Biochemistry & Cell Biology, Volume 43, Issue 7, July 2011, Pages 969-980Sybille Mazurek • PKM2 and the Tricky Balance of Growth and Energy in CancerMolecular Cell, Volume 42, Issue 6, 24 June 2011, Pages 713-714Andrew N. Macintyre, Jeffrey C. Rathmell

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