7.5 Metabolism without Oxygen

Anaerobic Cellular Respiration and Fermentation

Anaerobic respiration and fermentation keep cells producing ATP when oxygen isn't available. These pathways are far less efficient than aerobic respiration, but they're critical for survival in low-oxygen environments. Both begin with glycolysis, and the key challenge they solve is the same: regenerating $NAD^+$ so glycolysis can keep running.

Anaerobic Respiration vs. Fermentation

Both anaerobic respiration and fermentation occur without oxygen, and both depend on glycolysis as their starting point. Glycolysis breaks glucose into two pyruvate molecules ($C_3H_4O_3$), producing a net gain of 2 ATP and 2 NADH. The ATP here comes from substrate-level phosphorylation, where a phosphate group is transferred directly from a substrate molecule to ADP.

Where these two pathways diverge is what happens after glycolysis.

Anaerobic cellular respiration:

• Found in some prokaryotes, such as certain strains of Escherichia coli
• Still uses an electron transport chain, but instead of oxygen, the final electron acceptor is an inorganic molecule like sulfate ($SO_4^{2-}$), nitrate ($NO_3^-$), or carbonate ($CO_3^{2-}$)
• Produces more ATP than fermentation (variable, but generally fewer than the ~30–32 ATP from aerobic respiration)

Fermentation:

• Found in both prokaryotes and eukaryotes, including yeast (Saccharomyces cerevisiae) and human muscle cells
• Does not use an electron transport chain at all
• Uses an organic molecule (pyruvate or a derivative of it) as the electron acceptor
• Yields only the 2 ATP from glycolysis, with no additional ATP production
• Its main purpose is to regenerate $NAD^+$ so glycolysis can continue

Lactic Acid Fermentation in Animals

Lactic acid fermentation occurs in animal cells, especially in muscle cells during intense exercise (like sprinting) or any time oxygen delivery can't keep up with demand (hypoxia).

The process:

1. Glycolysis produces 2 ATP, 2 NADH, and 2 pyruvate
2. Without oxygen available, NADH donates its electrons to pyruvate, reducing it to lactic acid ($C_3H_6O_3$)
3. This oxidizes NADH back to $NAD^+$, which returns to glycolysis to accept more electrons

Why it matters physiologically:

• It lets muscle cells keep producing ATP and contracting even when oxygen is limited
• Lactic acid buildup lowers the pH in muscle tissue, contributing to the burning sensation and fatigue during hard exercise. (Note: the relationship between lactic acid and delayed onset muscle soreness, or DOMS, is more complex than once thought. DOMS is now attributed mainly to microscopic muscle damage, not just lactate accumulation.)
• The liver can recycle lactic acid back into glucose through the Cori cycle: lactic acid travels via the blood to the liver, gets converted back to pyruvate, and then to glucose, which can return to the muscles

Alcohol Fermentation in Yeast

Alcohol fermentation occurs primarily in yeast and is the basis for making bread, beer, and wine.

The process:

1. Glycolysis produces 2 ATP, 2 NADH, and 2 pyruvate
2. Pyruvate is decarboxylated (loses a $CO_2$) to form acetaldehyde ($C_2H_4O$). The enzyme pyruvate decarboxylase catalyzes this step.
3. NADH reduces acetaldehyde to ethanol ($C_2H_5OH$). The enzyme alcohol dehydrogenase catalyzes this step, and $NAD^+$ is regenerated.

Products:

• Ethanol (the alcohol in beer and wine)
• $CO_2$ (the gas that makes bread rise and beer fizzy)
• 2 ATP from glycolysis

Notice that alcohol fermentation has an extra step compared to lactic acid fermentation: the decarboxylation of pyruvate. That's why it releases $CO_2$ as a byproduct while lactic acid fermentation does not.

Redox Reactions and Anaerobic Metabolism

All of these pathways depend on redox reactions, where electrons are transferred between molecules. One molecule gets oxidized (loses electrons) while another gets reduced (gains electrons). In fermentation, NADH is oxidized back to $NAD^+$ when it donates electrons to pyruvate (or acetaldehyde). That electron transfer is the whole point.

Unlike aerobic respiration, fermentation does not use an electron transport chain. Anaerobic respiration does use one, but with a different final electron acceptor than oxygen.

Organisms vary in how they handle oxygen:

• Facultative anaerobes can switch between aerobic and anaerobic metabolism depending on whether oxygen is available. Yeast is a classic example: it respires aerobically when oxygen is present but ferments when it's not.
• Obligate anaerobes can only survive without oxygen. Oxygen is actually toxic to them, and they rely entirely on anaerobic pathways.