Problem Set 6, Problem 2: Mechanism of Phosphoglycerate Mutase

TL;DR

Phosphoglycerate mutase is an enzyme that catalyzes the conversion of 3-phosphoglycerate to 2-phosphoglycerate in glycolysis, using a phosphorylated histidine in its active site. The use of phosphoenolpyruvate as a phosphate donor for the enzyme is thermodynamically and structurally feasible, but it can temporarily disrupt ATP production in glycolysis.

Transcript

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Key Insights

• ❓ Phosphoglycerate mutase is an important enzyme in glycolysis, catalyzing the conversion of 3-phosphoglycerate to 2-phosphoglycerate.
• 😒 It uses a phosphorylated histidine in its active site, forming a rare phosphorous-nitrogen bond.
• 👥 Phosphoenolpyruvate can potentially transfer its phosphate group to phosphoglycerate mutase, but this disrupts ATP production temporarily in glycolysis.
• ❓ The proposed transformation between phosphoenolpyruvate and phosphoglycerate mutase is both thermodynamically and structurally feasible.

Questions & Answers

Q: How does phosphoglycerate mutase catalyze the conversion of 3-phosphoglycerate to 2-phosphoglycerate?

Phosphoglycerate mutase utilizes a phosphorylated histidine in its active site to transfer the phosphate group from the 3 position of glycerate to the 2 position, generating 2,3-bisphosphoglycerate. The phosphate group from the enzyme is then transferred back to the histidine to form 2-phosphoglycerate, regenerating the phosphoenzyme.

Q: Is the proposed transformation between phosphoenolpyruvate and phosphoglycerate mutase feasible?

Yes, both thermodynamically and structurally. Phosphoenolpyruvate contains a high-energy phosphate bond and resembles 2-phosphoglycerate, allowing it to fit into the active site of the enzyme. The keto-enol tautomerization equilibrium of pyruvate released during hydrolysis drives the transformation strongly to the right.

Q: What are the implications of using phosphoenolpyruvate to phosphorylate phosphoglycerate mutase on ATP production in glycolysis?

Initially, using phosphoenolpyruvate for phosphorylation disrupts ATP production at the pyruvate kinase step. However, since enzymes in glycolysis are present in catalytic amounts, once the entire pool of phosphoglycerate mutase is phosphorylated, phosphoenolpyruvate becomes available again for ATP production.

Q: How can phosphoenolpyruvate be produced if it is used to phosphorylate phosphoglycerate mutase?

Phosphoenolpyruvate can be produced through other pathways, such as gluconeogenesis, where pyruvate is converted to oxaloacetate and then to phosphoenolpyruvate using PEP carboxykinase (PEPCK). This allows glycolysis to proceed normally.

Summary & Key Takeaways

• Phosphoglycerate mutase is the eighth enzyme in the glycolysis pathway, catalyzing the conversion of 3-phosphoglycerate to 2-phosphoglycerate.

• The enzyme utilizes a phosphorylated histidine in its active site, forming a phosphorous-nitrogen bond, which is rare in biochemistry.

• Phosphoenolpyruvate, a high-energy phosphate compound, can potentially transfer its phosphate group to phosphoglycerate mutase, but this results in a temporary disruption of ATP production in glycolysis.