Gluconeogenesis localization: which characteristic enzyme of gluconeogenesis is not found in the cytosol (it is mitochondrial)?

Introduction / Context:
Gluconeogenesis uses enzymes distributed across cellular compartments. Understanding where each step occurs is crucial for predicting regulation and metabolite transport. This item focuses on identifying a core gluconeogenic enzyme that is not cytosolic.

Given Data / Assumptions:

• Several gluconeogenic reactions occur in the cytosol.
• Certain steps are localized to organelles to facilitate regulation and substrate channeling.
• We apply Recovery-First Policy to clarify the intent as a single-best answer question.

Concept / Approach:
Pyruvate carboxylase catalyzes pyruvate → oxaloacetate in the mitochondrial matrix and requires biotin and acetyl-CoA as an allosteric activator. Fructose-1,6-bisphosphatase is a cytosolic bypass enzyme. Glucose-6-phosphatase is associated with the endoplasmic reticulum membrane with its catalytic face in the ER lumen, functionally non-cytosolic but not mitochondrial. The question asks for a characteristic enzyme that is not in cytosol and highlights the mitochondrial resident as the single-best answer.

Step-by-Step Solution:
1) List enzyme localizations: PC (mitochondrial), F-1,6-BPase (cytosolic), G-6-Pase (ER membrane/lumen).2) Identify the one explicitly mitochondrial enzyme among the options: pyruvate carboxylase.3) Select pyruvate carboxylase as the single-best answer satisfying “not cytosolic (mitochondrial).”

Verification / Alternative check:
Mitochondrial biotin enzymes, including pyruvate carboxylase, are well characterized; deficiency syndromes and isotope tracing support its matrix localization and role in anaplerosis and gluconeogenesis.

Why Other Options Are Wrong:
Fructose-1,6-bisphosphatase is primarily cytosolic. “Both (a) and (b)” fails because (b) is cytosolic. Glucose-6-phosphatase is non-cytosolic but ER-associated rather than mitochondrial; the prompt seeks a single-best selection. Cytosolic PEPCK isoform, when present, is cytosolic by definition.

Common Pitfalls:
Conflating “not cytosolic” with “mitochondrial”; ER localization is also non-cytosolic but is a separate compartment. The question aims for the mitochondrial step specifically.

Final Answer:
Pyruvate carboxylase