Another highly regulated enzyme in glycolysis is phosphofructokinase (PFK1). There is evidence from some tumors that PFK1...

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  1. Another highly regulated enzyme in glycolysis isphosphofructokinase (PFK1). There is evidence from some tumors thatPFK1 undergoes a posttranslational proteolysis that yields atruncated functional enzyme (47 kD vs 85 kD) that is insensitive tocitrate and ATP. How might this work and why would it be beneficialfor a tumor cell?
  2. Several isoforms of pyruvate kinase (PK) exist, including PK-M2which exists mainly in embryonic and adult stem cells. PK-M2 hasalso been found in many tumor cells, but is in an inactive state.Explain why this seemingly counter-intuitive discovery is actuallya benefit for tumor cells.
  3. What is the normal function of pyruvate dehydrogenase kinase(PDK)?
  4. PDK is more active in cancer cells than regular cells due tothe presence of the HIF-1a transcription factor. Why is increasedactivity of PDK beneficial to cancer cells?

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1 Phosphofructokinase is an enzyme that phosphorylates fructose 6 phosphate to fructose 1 6 bisphosphate in presence of ATP This enzyme is an allosteric enzyme that is regulated by ATP and citrate ATP binds to both active site and regulatory site and this will cause inhibition of enzyme activity However if it only binds to ATP when level of ATP is low it will cause phosphorylation of fructose 6 phosphate due to ATP hydrolysis Increase citrate will increase ATP levels as it enters TCA cycle Thus high citrate and ATP will inhibit PFK    See Answer
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