Question

Phosphoglycerate dehydrogenase is involved in the synthesis of Ser.  The level of this enzyme is very high...

Phosphoglycerate dehydrogenase is involved in the synthesis of Ser.  The level of this enzyme is very high in some cancer types thus causing an increase on Ser in these cancer cells.   Cancer cells with increased Ser show an increase in flux through the TCA cycle. Explain.

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Answer #1

Phosphoglycerate dehydrogenase (PHGDH) is an enzyme that catalyses conversion of 3-phosphoglycerate to 3-phosphohydroxypyruvate which is committed step in the biosynthesis of L-Serine. Committed step is the step which indicates that the Serine will be formed once 3-phosphohydroxypyruvate is formed. Now, end product of this pathway, i.e. Serine is the inhibitor of PHGDH enzyme which means 3-phosphoglycerate will not be converted into 3-phosphohydroxypyruvate. Now, if you remember, 3-phosphoglycerate is a compound formed during glycolysis. If the flux towards the Serine production is stopped, then the flux through glycolysis will increase leading to increased amount of pyruvate. This will result in increase in the TCA cycle that will follow the glycolysis. So, in Cancer cells, the increase in Serine leads to increase in the flux through TCA cycle.

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