Question

In gluconeogenesis, the pyruvate to phosphoenolpyruvate is one of the bypass steps that is different from the reverse reaction in glycolysis due to the irreversible nature of pyruvate kinase. There are two pathways for this bypass reaction that differ in the location where the final PEP product is synthesized – either in the mitochondria or in the cytoplasm. Assume that your cell is undergoing gluconeogenesis using pyruvate derived from the deamination of serine by the enzyme serine dehydratase:
L-serine → Pyruvate + NH3
Which of the two pathways of phosphoenolpyruvate synthesis will be used and why? What are the intermediate steps for this reaction, and where do they occur?

Answer 1

L-serine → Pyruvate + NH3

This reaction occurs in liver cell cytoplasm. the pyruvate produced will undergo gluconeogenesis. It is transported to mitochondrial matrix. There it undergoes following reactions.

1. the pyruvate is converted to oxaloacetate by pyruvate carboxylase (mitochondria)

2. Oxaloacetate is converted to malate by malate dehydrogenas an enzyme present both in cytosol and mitochondria. This reaction occurs because mitochondrial membrane is impermeable to oxaloacetate but permeable to malate.

3. Malate is transported to cytosol and again converted to Oxalo acetate by same malate dehrydogenase.

4. Malate is converted to PEP by PEPcarboxy kinase. (cytosol)

5.PEP enters into gluconeogenesis.

Note: In cells which have PEPcarboxy kinase in mitochondria directly oxaloacetate is converted to PEP and transported to cytosol and enter gluconeogenesis.