Question

1. Several isoforms of pyruvate kinase (PK) exist, including PK-M2 which exists mainly in embryonic and adult stem cells. PK-M2 has also been found in many tumor cells, but is in an inactive state. Explain why this seemingly counter-intuitive discovery is actually a benefit for tumor cells.

2. What is the normal function of pyruvate dehydrogenase kinase (PDK)?

3. PDK is more active in cancer cells than regular cells due to the presence of the HIF-1a transcription factor. Why is increased activity of PDK beneficial to cancer cells?

4. Succinate and fumarate have been shown to accumulate in some cancer cells. Dysregulation of which two CAC cycle enzymes are most likely implicated in this accumulation?

Answer 1

1. PK-M2 is the potential target for regulating cancer to the growth of tumor cells. It also regulates both post-translation and allosteric regulators. Pyruvate kinase M2 is the isoenzyme of Pyruvate enzyme which is expressed in proliferating cells like embryonic cells and cancer cells. PK - M2 regulates cancer progression by regulating metabolic and non-metabolic pathways. PK - M2 also regulates the growth of tumor cells by regulating the expression of a gene that involves cell proliferation, migration, and apoptosis.

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2. Pyruvate dehydrogenase kinase is a mitochondrial enzyme that gets activated during cancers and results in selective inhibition of pyruvate dehydrogenase which is an enzyme helps in conversion cytosolic pyruvate to mitochondrial acetyl - CoA. Pyruvate dehydrogenase kinase is a kinase enzyme which inactivate the enzyme pyruvate dehydrogenase by phosphorylating it using ATP.

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3. Cancer cell required much more molecules to support there continuous groth and proliferation so they alter certain metabolism to support that unitteraption growth. So glucose metabolism is the moste frequently reprogammed by cancer cell in additon to fatty acid , amino acid and glutamine metabolism. So Pyruvate Dehydrogenase kinase use as gatechecker enzyme which altered glucose metabolism in cancer or tumor cells, which benifit continuosly growthof cancel cell without bothering of anergy. Higher cocnentration of PDK leads to shift in glucose metabolsim toward glycolysis instdwead of oxidative phosphorlaytion.

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4. Sucinyl-CoA synthaatase which catalyzes the reversible reaction of succinlye CoA to succinate. Succinate dehydrogenase enzyme which catalyzes the oxidation of succinate to fumarate.