Cell respiration

📚The biology

ATP: the energy currency

ATP stands for adenosine triphosphate. It is a nucleotide: the base adenine and the sugar ribose, attached to a chain of three phosphate groups. Its properties suit it to distributing energy in cells:

• it is soluble in water, so it moves easily through the cytoplasm to wherever energy is needed;
• it is stable at the pH of cells, so it does not break down unless an enzyme catalyses it;
• the energy released by removing one phosphate is a convenient, moderate amount — sufficient for many tasks, with little wasted;
• it cannot pass through membranes by diffusion, so each compartment keeps its own supply;
• it is rapidly regenerated from ADP and phosphate.

What ATP is used for

ATP and ADP

When ATP is hydrolysed, the terminal phosphate is removed, producing ADP (adenosine diphosphate) and a phosphate, and energy is released. To synthesize ATP from ADP and phosphate, energy is required — supplied by respiration (or, in chloroplasts, by light).

ATP is not a long-term store. A cell holds only a few seconds’ supply and recycles each molecule many times a minute.

Cell respiration

Cell respiration is the controlled release of energy from carbon compounds in cells, used to produce ATP. The principal substrates are glucose and fatty acids, but a wide range of carbon compounds, including amino acids, can be used.

Aerobic and anaerobic respiration in humans

Humans use anaerobic respiration when oxygen cannot be supplied fast enough, for example in muscles during short, intense exercise such as a sprint. It provides ATP quickly, but only a little per glucose, and lactate builds up.

Variables affecting the rate of respiration

The rate of respiration can be measured by the uptake of oxygen, the production of carbon dioxide, or the loss of mass of the substrate or organism. Variables that affect it include temperature (respiration is enzyme-controlled), the type and availability of substrate, oxygen concentration, and the activity of the organism.

A respirometer measures oxygen uptake. Small organisms such as germinating seeds or woodlice are placed in a sealed tube with a chemical (such as soda lime or potassium hydroxide) that absorbs carbon dioxide. As the organisms take in oxygen, the gas volume decreases, and a drop of coloured liquid moves along a capillary tube towards them. The distance moved per minute, converted to a volume, gives the rate of oxygen uptake. A control tube with glass beads instead of organisms corrects for changes in temperature and pressure.

NAD and oxidation AHL

Oxidation is the loss of electrons; reduction is the gain of electrons. In respiration, substrates are oxidized by removing hydrogen atoms — each hydrogen atom brings its electron with it — a process called dehydrogenation. Oxidation and reduction always happen together: these are redox reactions.

The hydrogen removed is accepted by the coenzyme NAD, which is reduced. Reduced NAD carries the hydrogen (and its energy-rich electrons) to the electron transport chain.

Glycolysis AHL

Glycolysis happens in the cytoplasm and does not need oxygen. It converts one glucose (6C) into two pyruvate (3C) in a series of steps, each catalysed by a different enzyme. Four stages:

1. Phosphorylation. Two phosphate groups are added to glucose, using 2 ATP. This makes the sugar less stable and ready to split.
2. Lysis. The 6C sugar phosphate splits into two 3C sugar phosphates (triose phosphate).
3. Oxidation. Hydrogen is removed from each 3C molecule and accepted by NAD, producing 2 reduced NAD.
4. ATP formation. Each 3C molecule is converted to pyruvate, releasing energy used to form 2 ATP per 3C molecule — 4 ATP in all.

Net yield per glucose: 4 ATP made − 2 ATP used = 2 ATP, plus 2 reduced NAD and 2 pyruvate.

Anaerobic respiration: regenerating NAD AHL

A cell contains only a small amount of NAD. If glycolysis continued without the reduced NAD being turned back into NAD, NAD would run out and glycolysis would stop. Without oxygen, the electron transport chain cannot do this, so another route is needed: pyruvate accepts the hydrogen from reduced NAD.

• In humans, pyruvate is reduced to lactate. NAD is regenerated, glycolysis continues, and the net yield is 2 ATP per glucose.
• In yeast, pyruvate is first decarboxylated, releasing carbon dioxide, and the product is reduced to ethanol. Again NAD is regenerated and the net yield is 2 ATP.

The pathways in humans and yeast are the same up to pyruvate; they differ only in how NAD is regenerated, and so in the final products.

The link reaction AHL

When oxygen is available, pyruvate enters the mitochondrial matrix. In the link reaction, each pyruvate (3C) is:

• decarboxylated — a carbon is removed as CO₂;
• oxidized — hydrogen is removed, forming reduced NAD;

leaving a 2C acetyl group, which is attached to coenzyme A to form acetyl-CoA. Coenzyme A delivers the acetyl group to the Krebs cycle. Both carbohydrates and lipids are broken down to acetyl groups, so this is the point where their pathways meet.

The Krebs cycle AHL

The Krebs cycle takes place in the matrix. You need to name only two intermediates.

1. The acetyl group (2C) is transferred from coenzyme A to oxaloacetate (4C), forming citrate (6C).
2. Citrate is converted back to oxaloacetate in a series of reactions that include two decarboxylations, releasing 2 CO₂, and four oxidations. The oxidations are dehydrogenations: hydrogen is removed and accepted by hydrogen carriers, mostly NAD (3 reduced NAD) and one other carrier.
3. One ATP is produced directly.
4. Oxaloacetate is regenerated, ready to accept another acetyl group.

Each glucose gives two pyruvate, so the cycle turns twice per glucose. By the end of the Krebs cycle, all six carbons of glucose have been released as CO₂ (two in the link reaction, four in the Krebs cycle), and most of the energy is now held in reduced NAD.

The electron transport chain AHL

Reduced NAD from glycolysis, the link reaction and the Krebs cycle carries its energy to the electron transport chain, a series of electron carrier proteins in the inner mitochondrial membrane.

• Reduced NAD passes a pair of electrons to the first carrier, and is converted back to NAD. This transfers energy to the chain.
• The electrons pass from carrier to carrier, releasing energy at each step.
• That energy is used by some carriers to pump protons (H⁺) from the matrix across the inner membrane into the intermembrane space, building a proton gradient: a high concentration of protons in the small intermembrane space.

Chemiosmosis AHL

Protons can only diffuse back into the matrix through channels in the enzyme ATP synthase, which spans the inner membrane. As protons flow down their concentration gradient through ATP synthase, the energy released makes part of the enzyme rotate, which drives the phosphorylation of ADP to ATP. This coupling of a proton gradient to ATP synthesis is chemiosmosis. It produces most of the ATP from aerobic respiration.

Oxygen as the terminal electron acceptor AHL

At the end of the chain, oxygen accepts the electrons, together with protons from the matrix, forming water (metabolic water). By removing electrons from the last carrier, oxygen allows electrons to keep flowing along the chain. Without oxygen, the carriers stay reduced, the chain stops, no more NAD is regenerated, and the link reaction and Krebs cycle stop too. That is why aerobic respiration depends on oxygen, even though oxygen is used only at the very last step.

Lipids and carbohydrates as substrates AHL