Shuttling Cytosolic NADH—Malate–Aspartate Shuttle Sites In which tissues is the malate–aspartate shuttle especially active for transferring cytosolic reducing equivalents into mitochondria?

Introduction / Context:
The inner mitochondrial membrane is impermeable to NADH. Cells therefore use shuttles to transfer the reducing power of cytosolic NADH into the mitochondrial matrix for oxidative phosphorylation. Two main systems exist: the malate–aspartate shuttle and the glycerol 3-phosphate shuttle. Tissue distribution differs and has metabolic consequences.

Given Data / Assumptions:

• Malate–aspartate shuttle is highly efficient (yields more ATP per cytosolic NADH).
• Heart and liver have high oxidative capacity and rely on efficient NADH transfer.
• Some skeletal muscles preferentially use the glycerol 3-phosphate shuttle.

Concept / Approach:
In the malate–aspartate shuttle, cytosolic oxaloacetate is reduced to malate using NADH; malate enters mitochondria via carriers, is reoxidized to oxaloacetate producing NADH in the matrix, and transamination with glutamate regenerates aspartate to complete the cycle. Heart and liver prominently use this shuttle to maximize ATP yield from cytosolic NADH.

Step-by-Step Solution:

Verification / Alternative check:
Biochemical measurements show higher malate–aspartate shuttle enzyme activities in heart and liver compared with tissues favoring the glycerol 3-phosphate shuttle.

Why Other Options Are Wrong:

• Lungs/pancreas/skin: not classic high-activity sites for this shuttle.
• “None of these” is incorrect because a specific pair is well established.

Common Pitfalls:
Assuming a single universal shuttle; in fact, shuttle choice varies by tissue and metabolic demand.

Final Answer:
Heart and liver