Location of the citric acid cycle — In eukaryotic cells, where does the Krebs (TCA) cycle operate?

Introduction / Context:
The Krebs, or tricarboxylic acid (TCA), cycle is the central hub of aerobic metabolism, oxidizing acetyl-CoA to CO2 while generating NADH and FADH2 for oxidative phosphorylation. Pinpointing its subcellular location is fundamental to understanding metabolic compartmentation.

Given Data / Assumptions:

• Eukaryotic cells have mitochondria containing an inner and outer membrane with a matrix compartment.
• Most TCA enzymes reside in the mitochondrial matrix; succinate dehydrogenase is embedded in the inner membrane (Complex II).
• Cytosol hosts glycolysis, not the TCA cycle.

Concept / Approach:
Map pathways to compartments: pyruvate is transported into mitochondria and converted to acetyl-CoA; the TCA cycle enzymes operate in the matrix, with reduced cofactors delivering electrons to the electron transport chain across the inner membrane.

Step-by-Step Solution:

Verification / Alternative check:
Biochemical fractionation localizes citrate synthase, isocitrate dehydrogenase, and other TCA enzymes to mitochondrial matrix fractions.

Why Other Options Are Wrong:

Common Pitfalls:
Assuming all metabolic pathways are cytosolic; overlooking compartment-specific regulation.

Final Answer:
Mitochondria (matrix).