Pathway ordering under anaerobic conditions: Which sequence correctly describes the order of events during the metabolism of glucose when molecular oxygen (O2) is absent?

Introduction / Context:
In the absence of oxygen, cells cannot use the mitochondrial electron transport chain as the terminal sink for electrons, and oxidative phosphorylation halts. Nevertheless, ATP must still be produced. This question asks for the correct ordering of processes that allow ATP generation under anaerobic conditions.

Given Data / Assumptions:

• Glycolysis can operate anaerobically to make a small amount of ATP via substrate-level phosphorylation.
• NAD+ must be regenerated from NADH to keep glycolysis running.
• Fermentation pathways regenerate NAD+ by reducing pyruvate to lactate (animals) or to ethanol and CO2 (yeast).

Concept / Approach:
First, glycolysis converts glucose to pyruvate, producing net ATP and NADH. Without O2, the TCA cycle and the electron transport chain cannot function as the main ATP sources. Fermentation follows to reoxidize NADH to NAD+, enabling continued glycolytic ATP production in the absence of oxidative phosphorylation.

Step-by-Step Solution:

Verification / Alternative check:
Measured cellular ATP levels during anoxia show reliance on glycolytic flux; inhibitors of lactate dehydrogenase or alcohol dehydrogenase under anaerobic conditions cause NAD+ depletion and arrest of glycolysis, confirming the sequence.

Why Other Options Are Wrong:

• Any option invoking oxidative phosphorylation or the citric acid cycle as functioning steps under strict anaerobiosis is incorrect because the respiratory chain is inactive without O2.
• Reversed or scrambled orders violate the dependency of fermentation on glycolysis-generated pyruvate and NADH.

Common Pitfalls:
Assuming the citric acid cycle can run meaningfully without an electron acceptor; its operation is tightly linked to the availability of oxidized cofactors produced by a functioning electron transport chain.

Final Answer:
Glycolysis → fermentation