Table of Contents
Fermentation is a set of catabolic pathways that allow cells to gain ATP from organic molecules in the absence of oxygen. It is always linked to glycolysis but differs from cellular respiration in what happens to the products of glycolysis.
General Principles of Fermentation
Under anaerobic conditions (no usable $O_2$):
- Glycolysis can still occur and produces:
- A small amount of ATP (substrate-level phosphorylation)
- Reduced coenzymes, mainly NADH
- Pyruvate (or similar 3‑carbon compounds)
- In the absence of an electron transport chain with $O_2$ as terminal electron acceptor:
- NADH cannot be reoxidized to NAD$^+$ by respiration
- Without NAD$^+$, glycolysis would stop
- Fermentation solves this by reducing an organic molecule (often pyruvate or a derivative) using NADH, thereby regenerating NAD$^+$
Essential points:
- Primary energy yield: ATP from glycolysis only
- Key role of fermentation: Regeneration of NAD$^+$ to keep glycolysis running
- Final electron acceptor: An organic molecule (not $O_2$, not an inorganic ion like in respiration)
Net ATP gain per glucose in fermentation is low (typically 2 ATP), in contrast to much higher yields in aerobic respiration.
Comparison: Fermentation vs. Cellular Respiration
Only aspects specific to the absence of oxygen and the fate of pyruvate are considered here.
In cellular respiration (with $O_2$):
- Pyruvate is fully oxidized to CO$_2$
- NADH and FADH$_2$ donate electrons to an electron transport chain
- $O_2$ is the final electron acceptor, forming H$_2$O
- A proton gradient across a membrane drives ATP synthase, generating many ATP
In fermentation (without $O_2$ or without an electron transport chain):
- Pyruvate (or derivative) is not fully oxidized
- NADH is reoxidized by transferring electrons to an organic acceptor
- End products are still energy-rich organic molecules (e.g., lactate, ethanol)
- No electron transport chain and no oxidative phosphorylation
- Low ATP yield; much of the potential energy remains in the waste products
Cells may switch between these modes depending on oxygen availability and their enzymatic equipment.
Functions and Ecological Significance of Fermentation
Fermentation is not just a “backup” process; it is a central energy-yielding strategy for many organisms and conditions.
- Survival in anoxic environments
- Sediments, waterlogged soils, animal intestines, deep wounds, and microenvironments in biofilms often lack $O_2$
- Many bacteria, yeasts, and some protists rely on fermentation there
- Rapid ATP supply for short bursts
- Some animal tissues switch to lactic acid fermentation during sudden intense activity when oxygen supply is insufficient
- Ecological interactions
- Fermentation products (e.g., organic acids, alcohols, gases) can:
- Serve as substrates for other microbes (syntrophy)
- Alter pH and environment (e.g., preservation by lactic acid)
- Influence community composition (selecting acid-tolerant species, methanogenic archaea, etc.)
- Economic and technological importance
- Food production (yogurt, cheese, bread, sauerkraut, kimchi, salami)
- Beverage production (beer, wine, cider)
- Industrial chemicals (ethanol, organic acids, solvents)
- Biogas production (CO$_2$, H$_2$, contribution to methane formation by other organisms)
Major Types of Fermentation
Many variants exist; for beginners, several main categories are especially important due to their biological, medical, and economic roles.
Lactic Acid Fermentation
In lactic acid fermentation, pyruvate is reduced to lactate by NADH:
$$
\text{pyruvate} + \text{NADH} + \text{H}^+ \rightarrow \text{lactate} + \text{NAD}^+
$$
Key features:
- No CO$_2$ is released from pyruvate in the final step
- NAD$^+$ regeneration enables ongoing glycolysis
- Occurs in:
- Many bacteria (e.g., lactic acid bacteria)
- Animal muscle cells (especially during strenuous exercise)
- Some fungi and protists
Homolactic vs. Heterolactic Fermentation
- Homolactic fermentation
- Main end product: lactate
- Typical equation (starting from glucose):
$$
\text{glucose} + 2 \ \text{ADP} + 2 \ \text{P}_i \rightarrow 2 \ \text{lactate} + 2 \ \text{ATP} + 2 \ \text{H}_2\text{O}
$$
- Performed by many Lactobacillus and Streptococcus species (important in dairy fermentations)
- Heterolactic fermentation
- Produces lactate plus other compounds: CO$_2$, ethanol and/or acetic acid
- Yields a mixture of products, influencing flavor and acidity of fermented foods
Alcoholic (Ethanol) Fermentation
Typical of many yeasts (e.g., Saccharomyces cerevisiae) and some bacteria.
Two main steps after glycolysis:
- Decarboxylation of pyruvate to acetaldehyde:
$$
\text{pyruvate} \rightarrow \text{acetaldehyde} + \text{CO}_2
$$ - Reduction of acetaldehyde to ethanol by NADH:
$$
\text{acetaldehyde} + \text{NADH} + \text{H}^+ \rightarrow \text{ethanol} + \text{NAD}^+
$$
Overall (from glucose):
$$
\text{glucose} + 2 \ \text{ADP} + 2 \ \text{P}_i \rightarrow 2 \ \text{ethanol} + 2 \ \text{CO}_2 + 2 \ \text{ATP} + 2 \ \text{H}_2\text{O}
$$
Biological and practical outcomes:
- Regeneration of NAD$^+$ keeps glycolysis active
- CO$_2$ gas forms bubbles (rising bread, carbonation in some drinks)
- Ethanol accumulates and can become toxic to most organisms at higher concentrations, giving yeast a competitive advantage up to their tolerance limit
Mixed Acid and Other Bacterial Fermentations
Many bacteria carry out more complex fermentations producing mixtures of acids, alcohols, and gases. Important examples:
Mixed Acid Fermentation
- Typical of many enteric bacteria (e.g., some Escherichia coli strains)
- End products: lactate, acetate, succinate, formate, ethanol, CO$_2$, H$_2$
- Contributes to the acidic environment in the gut and is used in microbiological tests to differentiate bacterial species
Propionic Acid Fermentation
- Performed by Propionibacterium species
- Converts lactate to propionate, acetate, and CO$_2$
- CO$_2$ bubbles cause “holes” (eyes) in certain cheeses (e.g., Emmental)
Butyric and Butanol Fermentations
- Seen in some Clostridium species
- Produce butyrate (butyric acid), butanol, acetone, isopropanol, CO$_2$, H$_2$
- Important in anaerobic decomposition of organic matter and in some industrial solvent productions
These diverse fermentation pathways illustrate how different enzyme sets and regulatory schemes lead to distinct end products and ecological niches.
Fermentation in Animals and Humans
Lactic Acid Fermentation in Muscle
When muscle cells work so intensively that oxygen supply cannot keep up:
- Pyruvate from glycolysis is reduced to lactate
- NAD$^+$ is regenerated, allowing ATP production in glycolysis to continue briefly
- This enables short, intense efforts (e.g., sprints) despite limited oxygen
Consequences:
- Lactate and protons accumulate, lowering pH in the muscle
- This contributes to fatigue and a burning sensation
- After exercise, when oxygen is available again:
- Lactate is transported to the liver or other tissues
- It can be converted back to pyruvate and further metabolized (e.g., by respiration or in metabolic cycles linking liver and muscle)
Microbial Fermentation in the Digestive Tract
Many animals, including humans, host fermenting microbes in their intestines:
- Microbes ferment otherwise indigestible carbohydrates (dietary fiber)
- End products (short-chain fatty acids like acetate, propionate, butyrate; gases like CO$_2$, H$_2$, sometimes CH$_4$ via other microbes) can:
- Serve as an energy source for the host
- Influence gut pH and microbiota composition
- Contribute to gas formation (flatulence)
Ruminants (e.g., cows, sheep) and some other herbivores rely heavily on microbial fermentation to gain energy from plant material.
Energetic and Evolutionary Aspects
Energetic Yield and Limitations
Fermentation pathways:
- Extract only a small fraction of the potential energy in glucose
- Result in energy-rich end products (e.g., lactate, ethanol), which still contain many C–H bonds
This low efficiency:
- Limits growth rates and biomass yield compared to organisms using full cellular respiration under similar conditions
- Is offset in some ecological settings by:
- Rapid throughput of substrate
- Simple enzymatic machinery (no respiratory chain, no specialized membranes)
- Independence from oxygen availability
Evolutionary Perspective
Points often proposed in evolutionary discussions:
- Fermentation uses simple enzymatic sequences and does not require molecular oxygen
- Many believe fermentation-like pathways could have been among the earliest forms of energy metabolism on an anoxic early Earth
- When oxygen became abundant, organisms that already ran glycolysis and fermentation could add respiratory chains, greatly increasing ATP yield
Fermentation remains advantageous:
- As a specialized adaptation to anoxic niches
- As a flexible backup for facultatively anaerobic organisms
- As a basis for many symbiotic relationships and biogeochemical processes
Industrial and Biotechnological Uses
Fermentation processes are exploited and optimized in many technologies:
- Food and beverage production
- Lactic acid fermentation: yogurt, kefir, cheese, pickled vegetables, fermented sausages
- Alcoholic fermentation: beer, wine, spirits (with subsequent distillation), bread (CO$_2$ leavening)
- Preservation
- Organic acids lower pH and inhibit spoilage organisms and pathogens
- Biofuels
- Ethanol production from plant biomass by yeasts and other microbes
- Bioproducts
- Production of organic acids (e.g., lactic, acetic, citric acids) and solvents
In these applications, conditions such as substrate type, temperature, pH, and oxygen availability are carefully controlled to favor desired fermentation pathways and products.
Summary of Key Features
- Fermentation is an anaerobic catabolic process that:
- Relies on glycolysis for ATP production
- Regenerates NAD$^+$ by reducing organic molecules (often pyruvate derivatives)
- Does not use an electron transport chain or $O_2$
- Main types include:
- Lactic acid fermentation (homolactic, heterolactic)
- Alcoholic (ethanol) fermentation
- Various bacterial fermentations (mixed acid, propionic, butyric, etc.)
- Fermentation is crucial:
- For life in anaerobic habitats
- During short-term oxygen limitation in animal tissues
- For numerous ecological processes and industrial applications