What happens after glycolysis in the presence of oxygen and in the absence of oxygen?

Question

Consider what the cell does with the products of glycolysis under different environmental conditions. When there's plenty of oxygen available, how might the cell continue extracting energy from glucose? Now, think about what happens when oxygen isn't present—what alternative pathway could the cell use to keep generating ATP and recycling necessary molecules?

Answer 1

In Aerobic conditions/Conditions with Oxygen we can follow glucose and its intermediates & outputs through the following cycles:

1. Glycolysis: Glucose --> Pyruvate, NADH, ATP
2. PDH (Pyruvate dehydrogenase complex): Pyruvate --> Acetyl-CoA, CO2, NADH
3. This step directly connects Glycolysis to the Citric Acid (TCA) cycle, but produces no energy
4. Citric Acid Cycle (TCA Cycle/Krebs Cycle): Acetyl-CoA --> CO2, NADH, FADH, GTP (ATP adjacent)
5. Electron Transport Chain (ETC) and Oxidative Phosphorylation: NADH, FADH --> ATP

The complete oxidation of 1 glucose yields 30-32 ATP in aerobic conditions.

In Anaerobic Conditions/Conditions lacking Oxygen, many of the metabolic cycles that rely on oxygen, whether directly or indirectly, cannot be used.

1. Glycolysis does not require oxygen, so the first step of glucose breakdown can be undergone as usual. Glucose is broken down to yield 2 pyruvate, 2 NADH (from NAD+), and 2 ATP (net).
2. Most anaerobic organisms use Fermentation to replenish the NAD+ that glycolysis requires. Fermentation converts NADH back into NAD+, stopping any NADH buildup that would prevent glycolysis from continuing (which would stunt ATP production). There are three types of fermentation: lactic acid, alcoholic, and mixed fermentation. Fermentation does not produce any ATP or energy, and only serves to replenish NAD+.
3. The *Electron Transport Chain requires oxygen (O2) as the terminal electron acceptor, so most organisms cannot run it when in hypoxic conditions (no oxygen). This also means that *Oxidative Phosphorylation, a mitochondrial processes that produces large amounts of ATP, can also not happen. However, there are a few species able to harness molecules other than oxygen as a terminal electron acceptor, with variation from species to species. These alternative compounds include sulfates, nitrates, and CO2. So, a handful of organisms are able to use both the ETC and oxidative phosphorylation to produce energy in low-oxygen conditions.
4. The Citric Acid Cycle indirectly relies on oxygen, so almost all anaerobic microbes avoid the TCA entirely.

Since different organisms use different forms of fermentation in the absence of oxygen, and many don't use the ETC and oxidative phosphorylation at all as well, the ATP yield per glucose molecule will vary from species to species. However, anaerobic energy production will always be less efficient than the aerobic way due to a lack of or less efficient usage of the TCA cycle and ETC.

Answer 2

After glycolysis, the fate of pyruvate—the end product of glycolysis—depends on whether oxygen is present in the cell's environment.

In the presence of oxygen (aerobic conditions):

Pyruvate is transported into the mitochondria, where it undergoes a transition step and is converted into a molecule called acetyl-CoA. This acetyl-CoA then enters the citric acid cycle (CAC), also known as the Krebs cycle. During this cycle, carbon atoms from acetyl-CoA are gradually oxidized, and high-energy electron carriers like NADH and FADH₂ are produced. These carriers hold onto electrons that are rich in energy. The NADH and FADH₂ molecules then move to the electron transport chain (ETC), a series of protein complexes embedded in the inner mitochondrial membrane.

not necessary to answer this question, but an important reminder about the ETC:

(In the ETC, the electrons are passed along the chain, and the energy released is used to pump protons across the membrane, creating a proton gradient. This gradient powers ATP synthase, an enzyme that generates large amounts of ATP—far more than glycolysis alone produces. Oxygen serves as the final electron acceptor at the end of the chain, combining with electrons and protons to form water. Without oxygen, this entire chain would back up and shut down, halting aerobic respiration).

In the absence of oxygen (anaerobic conditions):

Cells cannot carry out the citric acid cycle or electron transport chain effectively. Instead, pyruvate is diverted to an alternative process called fermentation. In many animal cells (such as human muscle cells), this means pyruvate is reduced to lactate (lactic acid). This reaction does not produce additional ATP directly, but it serves a critical purpose: it regenerates NAD⁺ from NADH.

This regeneration of NAD⁺ is essential because glycolysis relies on NAD⁺ to accept electrons during the breakdown of glucose. If NAD⁺ runs out, glycolysis—and therefore ATP production—would stop completely. So, fermentation allows glycolysis to continue even when oxygen is unavailable, by keeping a supply of NAD⁺ available. Although this process is much less efficient than aerobic respiration (producing only 2 ATP per glucose molecule), it's enough to keep the cell alive temporarily under low-oxygen conditions.