Step-by-Step Four Stages of Cellular Respiration Lesson Explained

Created by Editorial Team

The ProProfs editorial team is comprised of experienced subject matter experts. They've collectively created over 10,000 quizzes and lessons, serving over 100 million users. Our team includes in-house content moderators and subject matter experts, as well as a global network of rigorously trained contributors. All adhere to our comprehensive editorial guidelines, ensuring the delivery of high-quality content.

Learn about Our Editorial Process

Updated: May 20, 2025

Lesson

Lesson Overview

Stage 1: Glycolysis
Stage 2: Pyruvate Oxidation (Link Reaction)
Stage 3: Citric Acid Cycle (Krebs Cycle)
Stage 4: Oxidative Phosphorylation (Electron Transport Chain & Chemiosmosis)

Cellular respiration is the process by which cells convert glucose into ATP, the usable energy currency of the cell. It occurs in four main stages – glycolysis, pyruvate oxidation, the citric acid cycle, and oxidative phosphorylation – each with distinct roles and outputs.

Stage 1: Glycolysis

Glycolysis (meaning "sugar splitting") is the first stage of cellular respiration. It occurs in the cytoplasm and does not require oxygen (it is anaerobic).

During glycolysis, a 6-carbon glucose molecule is split into two 3-carbon pyruvate molecules through a series of enzyme-driven steps. The pathway has two phases: an energy investment phase (which uses up 2 ATP) followed by an energy payoff phase (which produces 4 ATP). This stepwise breakdown releases a small amount of energy, capturing it in ATP and in high-energy electrons carried by NADH. Glycolysis thus extracts some energy from glucose while preparing the pyruvate for the next stages.

Location: Cytoplasm of the cell.
Inputs: 1 glucose (6C), 2 ATP (to prime the process), 2 NAD⁺.
Outputs per glucose: 2 pyruvate (3C each), net 2 ATP (4 made − 2 used), and 2 NADH (electron carriers).
Key points: No O₂ is used in glycolysis, and no CO₂ is produced. Glycolysis can occur whether oxygen is present or not, making it the universal first step of both aerobic and anaerobic respiration. It provides the pyruvate and NADH that will feed into the aerobic pathways if oxygen is available.

Stage 2: Pyruvate Oxidation (Link Reaction)

Pyruvate oxidation (the "link reaction") bridges glycolysis and the citric acid cycle. It takes place in the mitochondrial matrix, where each pyruvate (from glycolysis) is converted into an acetyl-CoA molecule.

In this step, each pyruvate (3 carbons) is oxidized: a carboxyl group is removed and released as CO₂ (decarboxylation). The remaining 2-carbon fragment is attached to a large cofactor, coenzyme A, forming acetyl-CoA – this 2-carbon molecule will enter the citric acid cycle. During this conversion, NAD⁺ is reduced to NADH, capturing energy from the oxidation of pyruvate. Pyruvate oxidation does not produce ATP directly, but it yields the acetyl-CoA and NADH needed for the next stage. This reaction is facilitated by the multi-enzyme pyruvate dehydrogenase complex and is a crucial preparatory step for the Krebs cycle.

Location: Mitochondrial matrix (in eukaryotic cells). (In prokaryotes, which lack mitochondria, this occurs in the cytoplasm.)
Inputs: 2 pyruvate molecules per glucose, plus 2 NAD⁺ and 2 Coenzyme A (CoA).
Outputs per glucose: 2 acetyl–CoA (2C each), 2 CO₂, and 2 NADH. (Each pyruvate yields one CO₂ and one NADH as it becomes acetyl–CoA.)
Key points: No ATP is directly generated in this stage. Pyruvate oxidation essentially prepares the carbon fuel (acetyl-CoA) for the citric acid cycle and produces NADH that will be used in oxidative phosphorylation.

Take This Quiz:

Four Stages of Cellular Respiration! Trivia Quiz

Stage 3: Citric Acid Cycle (Krebs Cycle)

The citric acid cycle – also known as the Krebs cycle or tricarboxylic acid (TCA) cycle – is a cyclic pathway in the mitochondrial matrix that fully oxidizes the acetyl groups from acetyl-CoA into carbon dioxide. This cycle not only generates ATP but also produces the high-energy electron carriers needed for the final stage of respiration. It's called a "cycle" because the starting 4-carbon compound is regenerated at the end of each turn.

In each turn of the citric acid cycle, the 2-carbon acetyl group from acetyl-CoA is joined to a 4-carbon molecule oxaloacetate, forming a 6-carbon molecule citrate (citric acid). Through a series of enzyme-catalyzed steps, citrate is gradually broken back down to the 4-carbon oxaloacetate. Two carbon atoms are released as CO₂ along the way (these carbon atoms originally came from the acetyl group).

The cycle's redox reactions transfer energy to electron carriers: each acetyl-CoA that enters reduces 3 NAD⁺ to 3 NADH and 1 FAD to 1 FADH₂. In addition, 1 ATP (or an equivalent GTP) is produced per cycle turn by substrate-level phosphorylation. Since two acetyl-CoA molecules are produced from each glucose, the cycle runs twice per glucose molecule, yielding twice the amounts per glucose. This stage effectively harvests high-energy electrons and generates a small amount of ATP, while giving off CO₂ as waste.

Location: Mitochondrial matrix.
Outputs per acetyl-CoA (per one cycle turn): 2 CO₂, 3 NADH, 1 FADH₂, and 1 ATP (GTP).
Outputs per glucose (two turns): 4 CO₂, 6 NADH, 2 FADH₂, and 2 ATP in total from the cycle.
Key points: This cycle completes the oxidation of glucose. All six carbons from the original glucose have now been released as CO₂ (2 from pyruvate oxidation and 4 from the two turns of the cycle). The NADH and FADH₂ produced here contain most of the energy originally in glucose, now in the form of high-energy electrons. Oxygen is not used directly in the cycle's reactions, but this stage is aerobic-dependent – it will stop if oxygen is not available because NAD⁺ and FAD will not be regenerated (they get recycled by the electron transport chain using oxygen). The citric acid cycle is named for citrate, the first product, and Krebs for Hans Krebs who elucidated the pathway.

Stage 4: Oxidative Phosphorylation (Electron Transport Chain & Chemiosmosis)

Oxidative phosphorylation is the final stage of cellular respiration and generates the majority of the ATP. It takes place at the inner mitochondrial membrane and consists of two tightly linked components: the electron transport chain (ETC) and chemiosmosis. This stage uses the NADH and FADH₂ from the previous steps to power ATP synthesis, with oxygen serving as the crucial final electron acceptor.

In the electron transport chain, electrons from NADH and FADH₂ are transferred through a series of protein complexes and electron carriers embedded in the inner membrane. As these electrons move through the chain, they release energy. That energy is used to pump protons (H⁺) from the mitochondrial matrix into the intermembrane space, building up a proton gradient (a higher concentration of H⁺ outside the matrix).

After traveling through the chain, the low-energy electrons are finally passed to oxygen, which combines with these electrons and protons to form water (H₂O). Oxygen is essential here – without it, the electrons would have nowhere to go, and the whole process would back up and halt.

The proton gradient created by the ETC represents stored energy, like water behind a dam. In chemiosmosis, these protons flow back down their gradient into the matrix through an enzyme called ATP synthase. The flow of protons through ATP synthase drives the production of ATP from ADP and inorganic phosphate (Pi), much like a turbine generating power. This coupling of electron transport (driven by oxidation of NADH/FADH₂ and requiring oxygen) with phosphorylation of ADP is why the process is called oxidative phosphorylation. It produces a large yield of ATP compared to the earlier stages.

Location: Inner mitochondrial membrane (cristae).
Inputs: NADH and FADH₂ from glycolysis, pyruvate oxidation, and the citric acid cycle; O₂; ADP and Pi.
Outputs: NAD⁺ and FAD (recycled back as empty carriers), H₂O, and a large amount of ATP.
ATP yield: Each NADH can drive the production of about 2.5–3 ATP, and each FADH₂ about 1.5–2 ATP (FADH₂ contributes slightly less because it enters the ETC at a later point). Total ATP from oxidative phosphorylation is roughly 28–34 ATP per glucose. When combined with the 4 ATP produced earlier (2 from glycolysis, 2 from the citric acid cycle), the overall ATP yield of aerobic respiration can be up to ~32–38 ATP per glucose molecule under ideal conditions. (Actual yields in cells are often a bit lower due to losses and varying shuttle mechanisms.)
Key points: Oxidative phosphorylation is the stage that requires oxygen directly – if O₂ is lacking, the ETC stops, NADH/FADH₂ cannot unload their electrons, and ATP production beyond glycolysis ceases. This stage is the primary source of ATP in aerobic organisms, highlighting why oxygen is so critical for energy production.