CorpusHuman Anatomy
Cells & TissuesCell process

Cellular respiration

Also known as: glycolysis, Krebs cycle, citric acid cycle, TCA cycle, electron transport chain, oxidative phosphorylation, ATP synthase, chemiosmosis, link reaction, pyruvate dehydrogenase

The stepwise oxidation of glucose (and fats and amino acids) to CO₂ and water that captures energy as ATP: glycolysis in the cytosol, then the link reaction, citric-acid cycle and oxidative phosphorylation in mitochondria — ≈30–32 ATP per glucose.

Overview

ATP per glucose≈30–32 (2 from glycolysis, 2 from Krebs, ≈26–28 from OXPHOS)
ATP per NADH / FADH₂≈2.5 / ≈1.5
Reducing equivalents per glucose10 NADH + 2 FADH₂

1. Glycolysis (cytosol) splits one glucose (6C) into two pyruvate (3C), with a net gain of 2 ATP (substrate-level phosphorylation) and 2 NADH; it needs no oxygen. Key regulated step: phosphofructokinase-1. Without O₂ (or in cells without mitochondria, such as erythrocytes), pyruvate is reduced to lactate to regenerate NAD⁺, allowing glycolysis to continue.

2. Link reaction (mitochondrial matrix): the pyruvate dehydrogenase complex converts each pyruvate into acetyl-CoA + CO₂ + NADH (2 NADH per glucose); it requires thiamine (B1), lipoic acid, CoA (B5), FAD (B2) and NAD⁺ (B3). 3. Citric-acid (Krebs) cycle: acetyl-CoA (2C) joins oxaloacetate (4C) to form citrate (6C), which is oxidised back to oxaloacetate, releasing 2 CO₂. Per glucose (two turns): 6 NADH, 2 FADH₂, 2 GTP/ATP and 4 CO₂. Fatty acids (via β-oxidation) and many amino acids also feed in as acetyl-CoA or cycle intermediates.

4. Oxidative phosphorylation (inner mitochondrial membrane): NADH donates electrons to complex I, FADH₂ (via succinate dehydrogenase) to complex II; ubiquinone carries them to complex III, cytochrome c to complex IV, which reduces O₂ to water — oxygen is the final electron acceptor. Complexes I, III and IV pump protons into the intermembrane space, creating a proton-motive force; protons flowing back through ATP synthase (complex V) drive phosphorylation of ADP (chemiosmosis). Each NADH yields ≈2.5 ATP and each FADH₂ ≈1.5 ATP, giving a total of ≈30–32 ATP per glucose (the older figure of 36–38 assumed 3 and 2). Cytosolic NADH enters via the malate–aspartate shuttle (≈2.5 ATP) or the glycerol-3-phosphate shuttle (≈1.5 ATP), which explains the range.

Parts & subdivisions

  1. Glycolysis
    Glucose → 2 pyruvate; net 2 ATP + 2 NADH; cytosol; anaerobic.
  2. Pyruvate dehydrogenase (link reaction)
    Pyruvate → acetyl-CoA + CO₂ + NADH; matrix.
  3. Citric-acid cycle
    Per glucose: 6 NADH, 2 FADH₂, 2 GTP, 4 CO₂.
  4. Electron transport chain
    Complexes I–IV, ubiquinone and cytochrome c; pumps H⁺; O₂ → H₂O.
  5. ATP synthase (chemiosmosis)
    F₀F₁ rotary enzyme; ≈90 % of the ATP made from glucose.

Function

  • Supplies ATP for all energy-requiring processes.
  • Generates metabolic intermediates for biosynthesis.
  • Produces CO₂ (eliminated by the lungs) and metabolic water.
Physiology

Overall: C₆H₁₂O₆ + 6 O₂ → 6 CO₂ + 6 H₂O + ≈30–32 ATP. Respiration is controlled by demand: high ADP stimulates electron transport (respiratory control), while ATP, NADH and citrate inhibit key enzymes. An adult turns over roughly their own body weight of ATP each day, although only a few grams are present at any moment.

Clinical significance

Cyanide and carbon monoxide poisoning

Both inhibit complex IV (CO also displaces O₂ from haemoglobin): cells cannot use oxygen, so they shift to anaerobic glycolysis → lactic acidosis; with cyanide venous blood stays bright red because O₂ is not extracted. Treat cyanide with hydroxocobalamin (or nitrites + thiosulfate).

Lactic acidosis

Tissue hypoxia (shock, sepsis), mitochondrial disease, metformin toxicity and thiamine deficiency (PDH requires thiamine — e.g. alcoholics) increase lactate production.

Warburg effect

Cancer cells take up large amounts of glucose and ferment it to lactate even in the presence of oxygen (aerobic glycolysis); this is the basis of ¹⁸F-fluorodeoxyglucose (FDG) PET imaging.

Test yourself

Thermogenin (UCP1) generates heat in brown adipose tissue by:
  1. Hydrolysing ATP in the cytosol
  2. Letting protons re-enter the mitochondrial matrix without passing through ATP synthase
  3. Inhibiting cytochrome c oxidase
  4. Activating glycolysis anaerobically

Answer: Letting protons re-enter the mitochondrial matrix without passing through ATP synthase

UCP1 in the inner mitochondrial membrane uncouples oxidation from phosphorylation: the proton gradient is dissipated as heat. Brown fat is activated by sympathetic noradrenaline acting on β3-adrenergic receptors and is important in newborns.

More cells & tissues questions

Compiled from standard anatomy and physiology references — see the Cells & Tissues sources. For education only; not medical advice.