Revise Respiration for Cambridge 9700 (12.2)

Aerobic respiration occurs in the presence of oxygen and is the most efficient way to generate ATP from glucose. It's a complex metabolic pathway, typically divided into four main stages, each occurring in specific cellular locations.

C₆H₁₂O₆ + 6O₂ → 6CO₂ + 6H₂O + Energy (approx. 30-32 ATP)

Glycolysis, meaning 'sugar splitting', is the initial stage of both aerobic and anaerobic respiration. It occurs in the cytoplasm and does not require oxygen. During glycolysis, a molecule of glucose (6C) is phosphorylated using two ATP molecules (the energy investment phase), then split into two molecules of triose phosphate (3C). These are then oxidised to form two molecules of pyruvate (3C). This process generates a small net yield of ATP via substrate-level phosphorylation and reduces NAD⁺.

Following glycolysis, if oxygen is present, each pyruvate molecule moves from the cytoplasm into the mitochondrial matrix. Here, it undergoes the link reaction. Each pyruvate is decarboxylated (a carbon atom is removed as CO₂) and oxidised (loses hydrogen). The two-carbon molecule remaining, an acetyl group, combines with Coenzyme A to form acetyl CoA. For each pyruvate, 1 reduced NAD is produced. Since two pyruvate molecules are produced from one glucose, the link reaction generates 2 acetyl CoA and 2 reduced NAD per glucose molecule.

Also taking place in the mitochondrial matrix, the Krebs cycle is a cyclic series of reactions. Acetyl CoA (2C) combines with a 4-carbon compound (oxaloacetate) to form a 6-carbon compound (citrate). Through a series of decarboxylation and oxidation reactions, citrate is eventually regenerated to oxaloacetate, allowing the cycle to continue. For each turn of the cycle (i.e., per acetyl CoA), significant amounts of reduced coenzymes are produced.

This is where the vast majority of ATP is generated, occurring on the inner mitochondrial membrane (cristae). It involves two main processes: the electron transport chain and chemiosmosis.

The reduced NAD and reduced FAD molecules produced in previous stages donate their high-energy electrons to a series of electron carriers embedded in the inner mitochondrial membrane. As electrons pass along the chain, they release energy. This energy is used to actively pump protons (H⁺ ions) from the mitochondrial matrix into the intermembrane space, creating a high concentration of protons in this space. Oxygen acts as the final electron acceptor at the end of the chain, combining with electrons and protons to form water. This is why aerobic respiration requires oxygen!

The build-up of protons in the intermembrane space creates a proton electrochemical gradient (a potential energy store). Protons then flow down this gradient, back into the mitochondrial matrix, through specific channel proteins called ATP synthase. The flow of protons through ATP synthase drives the synthesis of ATP from ADP and inorganic phosphate (Pi) - a process known as chemiosmosis. This mechanism is similar to how hydroelectric dams generate electricity, using the flow of water to turn turbines.

Coenzymes are non-protein organic molecules that are essential for the function of certain enzymes. In respiration, they act as carriers for hydrogen atoms (protons and electrons) or acetyl groups. The main coenzymes are:

• NAD (nicotinamide adenine dinucleotide): A hydrogen carrier that accepts hydrogen atoms during oxidation reactions (becoming reduced NAD) and donates them during reduction reactions. The reaction is: $NAD⁺ + 2H⁺ + 2e^{-} ⇌ NADH + H⁺$.
• FAD (flavin adenine dinucleotide): Another hydrogen carrier, primarily used in the Krebs cycle. It accepts two hydrogen atoms: $FAD + 2H⁺ + 2e^{-} ⇌ FADH₂$.
• Coenzyme A (CoA): Carries the 2-carbon acetyl group, formed from pyruvate in the link reaction, to the Krebs cycle.

When oxygen is absent or in short supply, cells switch to anaerobic respiration. This pathway is far less efficient at producing ATP but allows glycolysis to continue by regenerating NAD⁺ from reduced NAD. This is crucial as glycolysis requires a constant supply of NAD⁺ to accept hydrogen from glucose.

During intense exercise, muscle cells may not receive enough oxygen. Pyruvate is converted into lactate (lactic acid) by accepting hydrogen from reduced NAD. This regenerates NAD⁺, allowing glycolysis to continue and produce a small amount of ATP. No further ATP is generated beyond glycolysis. Lactate accumulation lowers the pH, causing muscle fatigue and inhibiting enzymes.

In yeast and some plant tissues, pyruvate is first decarboxylated to form ethanal, releasing CO₂. Ethanal then accepts hydrogen from reduced NAD to form ethanol. This again regenerates NAD⁺ for glycolysis. This process is commercially important in brewing and baking.

While glucose is the primary respiratory substrate, cells can also respire lipids and proteins. The energy released per gram depends on the chemical composition of the substrate. Lipids contain a higher proportion of hydrogen atoms and a lower proportion of oxygen atoms compared to carbohydrates. This means more hydrogen atoms are available to reduce NAD and FAD, leading to more ATP production during oxidative phosphorylation. Consequently, lipids have a higher energy density.

• Carbohydrate: ~15.8 kJ g^{-1}
• Lipid: ~39.4 kJ g^{-1}
• Protein: ~17.0 kJ g^{-1}

The respiratory quotient (RQ) is the ratio of the volume of carbon dioxide produced to the volume of oxygen consumed during respiration. It can be used to determine the type of substrate being respired and whether respiration is aerobic or anaerobic.

$RQ = \frac{\text{Volume of } CO_2 \text{ produced}}{\text{Volume of } O_2 \text{ consumed}}$

Typical RQ values for aerobic respiration:

• Carbohydrates: 1.0 (e.g., for glucose, $6CO_2 / 6O_2 = 1.0$)$
• Lipids: ~0.7 (require more O₂ for their oxidation relative to CO₂ produced)
• Proteins: ~0.9

In anaerobic respiration, no oxygen is consumed. For ethanol fermentation where CO₂ is produced, the RQ is theoretically infinite ($RQ = CO_2 / 0 = \infty$). In lactate fermentation, no CO₂ is produced, so an RQ cannot be calculated.