Muscle metabolism during intense exercise: Lactic acid accumulates primarily because of a lack of which critical factor?

Introduction / Context:
During strenuous exercise, oxygen delivery can lag behind demand in working muscle. Cells then rely more on anaerobic pathways, leading to lactate formation. Understanding the trigger for this metabolic shift is key in exercise physiology.

Given Data / Assumptions:

• High ATP demand and limited oxygen supply in active muscle.
• Glycolysis continues to generate ATP rapidly.
• NAD+ must be regenerated to sustain glycolytic flux.

Concept / Approach:
When the electron transport chain slows due to insufficient O2 (the terminal electron acceptor), NADH cannot be reoxidized efficiently by oxidative phosphorylation. Cells regenerate NAD+ by reducing pyruvate to lactate via lactate dehydrogenase, enabling glycolysis to continue.

Step-by-Step Solution:
O2 scarcity limits electron flow at Complex IV in mitochondria.NADH oxidation slows, lowering available NAD+ for glyceraldehyde-3-phosphate dehydrogenase in glycolysis.Pyruvate is reduced to lactate, oxidizing NADH to NAD+ and sustaining ATP production.Therefore, the proximate cause for lactate accumulation is lack of oxygen.

Verification / Alternative check:
Measurements show increased lactate and decreased tissue O2 during peak exertion; lactate falls as O2 delivery and oxidative phosphorylation recover.

Why Other Options Are Wrong:

• NAD+: It is regenerated by lactate formation; the initial problem is limited O2.
• Glucose: Typically abundant from glycogen; not the immediate limiting factor.
• ADP and Pi: These accumulate to stimulate respiration; they are not lacking.

Common Pitfalls:
Assuming lactate is simply a “waste product”; it is also a valuable fuel and signaling molecule, shuttled to liver and heart.

Final Answer:
Oxygen