Question

Which of the following is correct sequence of steps involved in conversion of lactate to phosphoenolpyruvate

• A. Entry of lactate to mitochondria, conversion of lactate to pyruvate, conversion of pyruvate to oxaloacetate and entry into citric acid cycle, malate produced in citric acid cycle goes out of mitochondria, conversion of malate to oxaloacetate, conversion of oxaloacetate to phosphoenolpyruvate
• B. Conversion of lactate to pyruvate, conversion of pyruvate to oxaloacetate, entry of oxaloacetate into mitochondria and entry into citric acid cycle, malate produced in citric acid cycle goes out of mitochondria, conversion of malate to oxaloacetate, conversion of oxaloacetate to phosphoenolpyruvate
• C. Conversion of lactate to pyruvate, entry of pyruvate into mitochondria, conversion of pyruvate to oxaloacetate, conversion of oxaloacetate to malate, entry of malate into mitochondria and entry into citric acid cycle, conversion of malate to oxaloacetate, conversion of oxaloacetate to phosphoenolpyruvate
• D. Conversion of lactate to pyruvate, entry of pyruvate into mitochondria, conversion of pyruvate to oxaloacetate, conversion of oxaloacetate to phosphoenolpyruvate

Hint:

When lactate is the precursor, NADH is already available in the cytosol.
As a result, oxaloacetate is converted directly to PEP inside the mitochondria by mitochondrial PEPCK, bypassing the malate shuttle.

Answer 1

The Correct Option is D

Step 1: Understanding the Concept:
Gluconeogenesis is the metabolic pathway that synthesizes glucose from non-carbohydrate precursors, such as lactate, glycerol, and glucogenic amino acids.
The conversion of lactate to phosphoenolpyruvate (PEP) is the first major phase of gluconeogenesis, bypassing the irreversible pyruvate kinase step of glycolysis.

Step 2: Detailed Explanation:
The conversion of lactate to PEP occurs through a coordinated sequence of enzymatic steps across the cytosol and mitochondria:
Lactate in the cytosol is oxidized to pyruvate by the enzyme lactate dehydrogenase (LDH). This reaction also generates NADH in the cytosol.
Pyruvate then enters the mitochondria via a specific mitochondrial pyruvate carrier.
Inside the mitochondrial matrix, pyruvate is carboxylated to oxaloacetate (OAA) by the biotin-dependent enzyme pyruvate carboxylase, consuming one ATP molecule.
Since the conversion of lactate to pyruvate in step 1 already generated cytosolic NADH, there is no need to use the mitochondrial malate shuttle to transport reducing equivalents to the cytosol.
Instead, mitochondrial oxaloacetate is directly converted to phosphoenolpyruvate (PEP) inside the mitochondria by the mitochondrial isoform of phosphoenolpyruvate carboxykinase (PEPCK), consuming GTP.
PEP is then transported out of the mitochondria into the cytosol to continue along the gluconeogenic pathway.
This streamlined sequence corresponds to the path shown in Option (D).

Step 3: Final Answer:
The correct sequence is: Conversion of lactate to pyruvate, entry of pyruvate into mitochondria, conversion of pyruvate to oxaloacetate, and conversion of oxaloacetate to phosphoenolpyruvate.