Anaerobic Respiration

This lesson is mapped to AQA 7402 Section 3.5.1 — Anaerobic respiration in mammals, yeast, and plants (refer to the official AQA specification document for exact wording). When oxygen is unavailable or in limited supply, cells cannot run oxidative phosphorylation, and the bulk of the ~32 ATP per glucose yield is lost. Glycolysis, however, can continue — provided that NAD⁺ is regenerated from the NADH produced at step 5 of glycolysis. Anaerobic respiration is the collective name for the metabolic strategies that achieve this regeneration without oxygen as terminal electron acceptor. In doing so they enable a small but vital trickle of ATP (2 per glucose) that can sustain rapid bursts of muscular work in animals, allow yeast cells to ferment sugars in oxygen-poor brewing vats, and let waterlogged plant roots survive hypoxia.

The pathways have profound commercial and physiological importance. The brewing, baking, and wine industries depend on yeast ethanol fermentation, which has been exploited since at least 4000 BCE (Sumerian and Egyptian brewing records). Lactate fermentation underlies the production of yoghurt, cheese, sourdough, kimchi, and sauerkraut. And on the medical side, lactate accumulation in critically ill patients — measured as serum lactate — is one of the most sensitive markers of tissue hypoxia in modern intensive care.

Key Definition: Anaerobic respiration is the partial oxidation of glucose to release energy in the form of ATP without the use of oxygen as the terminal electron acceptor. NAD⁺ is regenerated from NADH by reducing pyruvate (or a derivative of pyruvate), allowing glycolysis to continue.

---

Why Anaerobic Respiration is Necessary

During glycolysis (step 5, the glyceraldehyde-3-phosphate dehydrogenase reaction), NAD⁺ is reduced to NADH + H⁺ when triose phosphate is oxidised. The cellular pool of NAD⁺ is small — typically about 1 mM. If NADH cannot be re-oxidised:

• Aerobically, the inner-membrane ETC re-oxidises NADH to NAD⁺ via Complex I (with O₂ as final acceptor).
• Anaerobically, this route is blocked. Without an alternative way to regenerate NAD⁺, the entire NAD⁺ pool would be exhausted within roughly 10 seconds of high glycolytic flux. Step 5 would stall, the substrate-level phosphorylation steps that follow it (steps 6 and 9) would also stall, and ATP production via glycolysis would cease.

Anaerobic pathways solve this problem by redirecting NADH onto pyruvate (or a derivative): pyruvate is reduced, NADH is oxidised back to NAD⁺, and glycolysis continues unchecked. This is a chemical trick of remarkable elegance: the cell sacrifices the energy that could have been extracted from pyruvate aerobically in order to keep glycolysis running.

---

Lactate Fermentation (in Mammals and Some Bacteria)

Process

• Occurs in the cytoplasm of animal cells (especially skeletal muscle during intense exercise), erythrocytes (which lack mitochondria entirely), and many bacteria (e.g. Lactobacillus, Streptococcus thermophilus).
• Pyruvate (3C) is reduced to lactate (3C) by the enzyme lactate dehydrogenase (LDH).
• NADH + H⁺ is the hydrogen donor and is oxidised back to NAD⁺ in the process.

Summary Equation

Pyruvate + NADH + H⁺ → Lactate + NAD⁺

Overall Equation from Glucose

Glucose → 2 Lactate + 2 ATP

Key Features

• Lactate fermentation is reversible — when oxygen becomes available again, lactate can be re-oxidised to pyruvate by lactate dehydrogenase running in the opposite direction.
• The lactate produced is transported in the blood plasma (as the lactate anion, since at physiological pH ~7.4 lactic acid is essentially fully dissociated) to the liver, where it is either:
  • Oxidised back to pyruvate (then to acetyl-CoA + Krebs cycle), or
  • Converted back to glucose via gluconeogenesis in the Cori cycle (liver glucose returns to muscle via the bloodstream; the cycle was elucidated by Carl and Gerty Cori, who shared the 1947 Nobel Prize).
• Accumulation of lactate produces an associated H⁺ (released by ATP hydrolysis that funded glycolytic flux), lowering muscle pH, contributing to fatigue, and altering the kinetics of muscle proteins and ion channels. The "burning sensation" of intense exercise has historically been attributed to lactate; more recent work suggests the H⁺ rather than the lactate itself is the principal cause.
• No CO₂ is produced during lactate fermentation — the carbon skeleton of pyruvate is preserved intact in lactate.

Exam Tip: Lactate fermentation produces no CO₂. This distinguishes it from ethanol fermentation. A common error is to write "lactate fermentation releases CO₂" — it does not.

graph LR
    A["Glucose"] -->|"Glycolysis<br/>2 ATP net, 2 NADH"| B["2 × Pyruvate (3C)"]
    B -->|"Lactate dehydrogenase<br/>NADH → NAD⁺"| C["2 × Lactate (3C)"]
    C -.->|"blood transport"| D["Liver: Cori cycle<br/>gluconeogenesis"]
    D -.->|"glucose back to muscle"| A

    style B fill:#3498db,color:#fff
    style C fill:#e67e22,color:#fff

---

Ethanol Fermentation (in Yeast and Some Plant Cells)

Process

• Occurs in the cytoplasm of yeast cells (Saccharomyces cerevisiae and other species) and some plant cells under anaerobic conditions (e.g. waterlogged roots).
• This is a two-step process:

1. Decarboxylation: Pyruvate (3C) → ethanal (acetaldehyde, 2C) + CO₂. Catalysed by pyruvate decarboxylase (a thiamine pyrophosphate-dependent enzyme).
2. Reduction of ethanal: Ethanal (2C) + NADH + H⁺ → ethanol (2C) + NAD⁺. Catalysed by alcohol dehydrogenase (ADH).

Summary Equations

Step 1: Pyruvate → Ethanal + CO₂

Step 2: Ethanal + NADH + H⁺ → Ethanol + NAD⁺

Overall Equation from Glucose

Glucose → 2 Ethanol + 2 CO₂ + 2 ATP

Key Features

• Ethanol fermentation is irreversible in yeast — pyruvate decarboxylase is essentially one-way. Yeast cannot convert ethanol back to pyruvate.
• CO₂ is produced (unlike lactate fermentation). In bread baking, this CO₂ inflates the dough; the ethanol evaporates during baking. In brewing, the CO₂ provides natural carbonation in cask ales or is allowed to escape in still wines.
• Ethanol is toxic to yeast cells at concentrations above ~14–15%, which sets an upper limit on natural wine alcohol content; distilled spirits exceed this only because distillation concentrates the ethanol after fermentation has stopped.
• This process is also used by some plant tissues (e.g. flooded rice paddies, fermenting fruit) and by anaerobic protists in marine sediments.

---

Comparison of Aerobic and Anaerobic Respiration

Feature	Aerobic Respiration	Lactate Fermentation	Ethanol Fermentation
Oxygen required	Yes	No	No
Location	Cytoplasm + mitochondria	Cytoplasm only	Cytoplasm only
End products	CO₂ + H₂O	Lactate	Ethanol + CO₂
ATP yield per glucose	~32 (theoretical max)	2 (net)	2 (net)
Glucose oxidation	Complete	Partial (incomplete)	Partial (incomplete)
NAD⁺ regeneration	Via ETC (electrons to O₂)	Via reduction of pyruvate	Via reduction of ethanal
Reversibility	N/A	Reversible (Cori cycle)	Irreversible
CO₂ produced	Yes (link + Krebs)	No	Yes (decarboxylation step)
Found in	Most eukaryotes; aerobic bacteria	Muscle, erythrocytes, Lactobacillus	Yeast, some plants

---

Oxygen Debt (Excess Post-exercise Oxygen Consumption — EPOC)

After a period of intense anaerobic exercise, an organism continues to breathe heavily and consume oxygen at an elevated rate even after exercise has stopped. This is because extra oxygen is needed to:

1. Re-oxidise lactate — lactate is transported to the liver (Cori cycle) and converted back to pyruvate, then to glucose (gluconeogenesis) or further oxidised aerobically. This requires oxygen.
2. Replenish ATP and phosphocreatine stores — phosphocreatine is the rapid ATP buffer of fast-twitch muscle and is depleted during sprint efforts.
3. Reoxygenate myoglobin and haemoglobin — restore oxygen reserves in muscle (myoglobin) and blood (haemoglobin).
4. Maintain elevated metabolic rate — heart rate, ventilation rate, and core body temperature remain elevated for several hours, all consuming oxygen.

Key Definition: Oxygen debt (EPOC — Excess Post-exercise Oxygen Consumption) is the additional oxygen consumed after exercise, above the resting level, required to metabolise accumulated lactate, replenish ATP and phosphocreatine, re-saturate myoglobin and haemoglobin, and restore pre-exercise conditions.

---

Respiratory Quotient (RQ)

The respiratory quotient is a ratio that indicates which respiratory substrate is being metabolised and whether respiration is wholly aerobic.

Formula

RQ = CO₂ produced ÷ O₂ consumed

RQ Values for Different Substrates

Substrate	RQ Value	Explanation
Carbohydrate (glucose)	1.0	C₆H₁₂O₆ + 6O₂ → 6CO₂ + 6H₂O (equimolar CO₂ and O₂)
Lipid (e.g. tripalmitin)	~0.7	Lipids have a much higher H:O ratio than carbohydrates; more O₂ is needed per CO₂ produced because more electron pairs must reach the ETC
Protein	~0.8	Intermediate; amino acids are deaminated before entering respiratory pathways via acetyl-CoA or Krebs cycle intermediates
Anaerobic respiration (ethanol)	>1.0 or undefined	CO₂ produced without O₂ consumption (ethanol fermentation in yeast/plants)
Anaerobic respiration (lactate)	0 for the anaerobic component	No CO₂ produced by lactate fermentation; if all respiration were lactate fermentation, RQ would be 0

Interpreting RQ Values

• RQ = 1.0 → carbohydrate is the main respiratory substrate (resting after a meal).
• RQ < 1.0 → lipid or protein is being respired (e.g. during fasting, prolonged endurance exercise, in hibernating animals).
• RQ > 1.0 → anaerobic respiration is occurring alongside aerobic respiration (extra CO₂ from ethanol fermentation; or hyperventilation washing out CO₂ stores).
• A rising RQ during exercise suggests a shift towards anaerobic respiration (particularly ethanol-type, though in animals this is lactate-type and the additional CO₂ comes from buffering the H⁺ associated with lactate).

Exam Tip: Be prepared to calculate RQ from respirometer experimental data (covered in detail in lesson 8). If given paired measurements of O₂ and CO₂ exchange, calculate the ratio and interpret what it indicates about the substrate being respired.

---

Specific Tissues and Their Anaerobic Capacity

Red Blood Cells

Mammalian erythrocytes lack mitochondria entirely — they extrude them during maturation, leaving only the cytosolic enzymes of glycolysis. Lactate fermentation is therefore their only route to ATP. The lactate produced is exported to plasma and metabolised by the liver. This explains why anaemia (low red cell count) and high altitude (low oxygen tension) both produce elevated systemic lactate.

Fast-Twitch (Type II) Skeletal Muscle Fibres

Type II fibres contain relatively few mitochondria and are optimised for rapid, powerful contractions over short timescales. They rely on glycolytic SLP for ATP during sprint efforts, accumulating lactate and producing the characteristic post-exercise oxygen debt. Slow-twitch (Type I) fibres, by contrast, are mitochondria-rich and rely on oxidative phosphorylation.

Flooded Plant Roots

When soil is waterlogged, the diffusion of O₂ to root tissue is severely restricted (oxygen diffuses 10⁴ times slower in water than in air). Many plants tolerate short-term flooding by switching root metabolism to ethanol fermentation. Rice (Oryza sativa) has evolved elaborate adaptations — including aerenchyma (gas-filled tissue) — that allow it to survive prolonged paddy submergence by combining residual aerobic respiration with ethanol fermentation.

---

Why Anaerobic Respiration is Less Efficient

• Anaerobic respiration yields only 2 ATP per glucose (from glycolysis), compared with ~32 ATP from aerobic respiration.
• Glucose is only partially oxidised — the remaining chemical energy is still trapped in the C–C and C–H bonds of lactate or ethanol. Lactate has a high enough energy content that the liver can recover it via the Cori cycle; ethanol's energy is largely wasted to yeast (though humans, of course, find a different use for it).
• The reduced coenzymes (NADH) produced in glycolysis are used to reduce pyruvate (or ethanal) rather than donating electrons to the ETC.
• This makes anaerobic respiration approximately 2/32 ≈ 6% as efficient as aerobic respiration in terms of ATP yield per glucose.
• The shortfall is the principal reason why anaerobic conditions limit the maximum sustained intensity and duration of muscular exertion.

---

Synoptic Links

This lesson connects to:

1. AQA 7402 Section 3.6.2 — Muscle contraction: fast-twitch (Type II) fibres rely on anaerobic glycolysis and lactate fermentation; slow-twitch (Type I) fibres are mitochondria-rich and aerobic. Phosphocreatine (PCr) buffers ATP during the first ~10 seconds of high-intensity exercise.
2. AQA 7402 Section 3.1.4 — Enzyme kinetics: lactate dehydrogenase exists as several isozymes (LDH-1 to LDH-5) with different tissue distributions and kinetic properties; serum LDH is a clinical marker for myocardial infarction and muscle injury.
3. AQA 7402 Section 3.6.4.2 — Glucose homeostasis: the Cori cycle links lactate metabolism in muscle to gluconeogenesis in liver, hormonally regulated by glucagon and insulin.

---

Common Errors and Mark-Loss Patterns