Citric Acid Cycle Localization—Eukaryotic Cells In eukaryotic cells, most enzymes of the tricarboxylic acid (TCA) cycle are located in which compartment?

Introduction / Context:
The tricarboxylic acid (TCA) cycle oxidizes acetyl-CoA to CO2 while capturing high-energy electrons in NADH and FADH2. Correct subcellular localization is foundational for understanding metabolic channeling and respiratory efficiency in eukaryotes.

Given Data / Assumptions:

• Eukaryotic mitochondria have an outer membrane, an inner membrane, an intermembrane space, and a matrix.
• Most soluble metabolic enzymes of the TCA cycle are not membrane-bound.

Concept / Approach:
With the exception of succinate dehydrogenase (Complex II), which is embedded in the inner mitochondrial membrane, TCA enzymes reside in the mitochondrial matrix. This compartmentalization brings them close to pyruvate dehydrogenase and to the electron transport chain that reoxidizes cofactors.

Step-by-Step Solution:

Verification / Alternative check:
Proteomic fractionation places TCA enzymes in the matrix; only succinate dehydrogenase is a transmembrane complex connecting TCA to the respiratory chain.

Why Other Options Are Wrong:

• Inner membrane/intermembrane space: house the electron transport chain and cytochrome c, not most TCA enzymes.
• Cytosol/nucleus: not sites of the mitochondrial TCA in eukaryotes.

Common Pitfalls:
Thinking “mitochondria” generally without specifying the matrix vs. membranes; the precise compartment matters.

Final Answer:
Mitochondrial matrix