Section III - Reasoning in Biological and Physical SciencesScientific literacyBiologyCellular respiration

Cellular respiration

The stages and processes involved in aerobic and anaerobic cellular respiration
5 min

Cellular respiration is a highly efficient catabolic pathway that converts glucose () and oxygen into :

Cellular respiration reaction in three stages: glycolysis, the Krebs cycle and the electron transport chain.

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Glycolysis occurs in the cytosol; it begins with the breakdown of glucose into two molecules of pyruvate.

Pyruvate then enters the mitochondrion, where it is converted into acetyl CoA and enters the Krebs cycle.

In the Krebs cycle, pyruvate is completely broken down into .

During both glycolysis and the Krebs cycle, there are multiple steps in which electron carrier molecules (, nicotinamide adenine dinucleotide and , flavin adenine dinucleotide) receive electrons, i.e. are reduced ( is reduced to , is reduced to ).

and then feed into the electron transfer chain, also within the mitochondrion. Electrons are released and combine with and to form water. This process releases energy, which is used to regenerate into .

An overview of the process is shown below.

OVERVIEW OF CELLULAR RESPIRATION. Cytoplasm: 1 Glucose, 2 ADP + 2 Pi, 2 NAD+, Glycolysis, 2 ATP, 2 NADH, 2 Pyruvate + 2 CoA, 2 NAD+, 2 NADH, 2 Acetyl-CoA, 2 ADP + 2 Pi, Krebs cycle, 2 ATP, 6 NAD+, 2 FAD, 6 CO2. Mitochondria: O2 + H+, ADP + Pi, Electron transfer chain, 6 H2O, 26-28 ATP.
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Glycolysis (‘sugar splitting’) is a ten-step metabolic pathway that breaks down one molecule of glucose, a 6-carbon sugar, into two molecules of pyruvate, a 3-carbon sugar as shown in the equation below.

Glycolysis also yields 2 and 2 molecules. This process occurs in the cytoplasm, does not require oxygen and does not release carbon dioxide. However, pyruvate and will only proceed to further stages of cellular respiration if oxygen is available.

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Glycolysis has two phases.

In the first, energy investment phase, two molecules of are consumed to prime glucose and intermediate substrates, increasing their reactivity.

In the second, energy payoff phase, intermediate substrates with very high potential energies are generated. As a result, 4 and 2 are generated.

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After glycolysis, pyruvate is actively transported into mitochondria and converted to a high-energy compound acetyl coenzyme A (acetyl CoA) via a three-step metabolic pathway, as shown in the equation below.

Acetyl CoA then proceeds to the Krebs cycle: a cyclic eight-step metabolic pathway, in which acetyl CoA reacts with oxaloacetate to form citrate, and is then oxidised in a stepwise manner. As its intermediates react, they donate electrons and hydrogen to reduce into , and into .

Although some is produced during the Krebs cycle, most of the potential energy from the original glucose molecule remains stored in and .

THE KREBS CYCLE. Acetyl CoA. Four-carbon acceptor molecule (regenerated in each cycle). Oxaloacetate. NADH. NAD+. Malate. Fumarate. Succinate. GTP. Pi. Energy-carrying molecule equivalent to ATP. Citrate. Six-carbon molecule formed from acetyl CoA + oxaloacetate. Isocitrate. α-ketoglutarate. One carbon lost as CO2. NAD+. NADH + CO2. Second carbon lost as CO2. NAD+. NADH.
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The Krebs cycle is so called because a substrate of its first reaction is a product of its final reaction.

When acetyl CoA (2-carbon compound) enters the cycle, it reacts with oxaloacetate (4-carbon compound) to produce citrate (6-carbon compound). During stepwise oxidation, citrate is converted into isocitrate, α-ketoglutarate (5-carbon compound), succinyl CoA (4-carbon compound), succinate, fumarate, malate and finally back into oxaloacetate again.

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The electron transfer chain is a collection of electron carrier proteins – cytochromes – embedded in the inner mitochondrial membrane.

and deliver and feed electrons into the electron transfer chain. As electrons travel down the chain, electron carrier proteins alternate between reduced and oxidised forms, accepting electrons from the previous protein and passing them onto the next.

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Cytochromes are arranged such that each one is slightly more electronegative (likely to accept electrons) than the previous one. The last cytochrome of the chain passes its electrons to oxygen, a very electronegative molecule, which then picks up a pair of protons and forms water, as shown in the equation below.

The purpose of the electron transfer chain is to break the large potential difference between and into smaller steps, ensuring that all the energy can be harnessed.

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The electron transport chain does not produce any . However, it uses the energy generated by redox reactions to pump protons from the mitochondrial matrix into the intermembrane space. This is a form of active transport that establishes a proton concentration gradient, called the proton-motive force.

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As protons attempt to return into the matrix, diffusing down their concentration gradient, they can only move through one transporter: the synthase.

These enzymes are ubiquitous in the inner mitochondrial membrane. They harness the energy of proton flow to synthesise from and inorganic phosphate; this process is called chemiosmosis.

Each molecule of glucose can fuel approximately 26–28 molecules of to be made by synthases in the inner mitochondrial membrane.

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The majority of inside cells is generated by cellular respiration, also called aerobic respiration, an oxygen-dependent process.

However, some cells can still generate without oxygen via anaerobic respiration.

Both types of respiration use glycolysis to oxidise glucose to pyruvate, yielding 2 molecules, using as the oxidising agent.

However, in the absence of oxygen, anaerobic respiration does not involve the Krebs cycle or the electron transfer chain.

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Anaerobic respiration can be divided into two major types:

  • Alcohol fermentation, which is mainly carried out in yeast, but also in other fungi and some bacteria
  • Lactic acid fermentation, which is mainly carried out in bacteria, especially the genus Lactobacillus, fungi, and some higher eukaryotes, including humans.
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In alcohol fermentation, pyruvate generated by glycolysis is further broken down to acetaldehyde, and then to ethanol, as shown in the equations below. Reduction of acetaldehyde to ethanol regenerates .

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In lactic acid fermentation, pyruvate is reduced to lactate, regenerating , as shown in the equation below.

Unlike alcohol fermentation, lactic acid fermentation does not release .

This process also occurs in human muscle cells when oxygen supply becomes insufficient during intense exercise. Excess lactate is carried away to the liver, converted back to pyruvate and enters the aerobic respiration pathway.

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A comparison of aerobic and anaerobic respiration pathways is given in the table below.

THE DIFFERENCES BETWEEN AEROBIC AND ANAEROBIC RESPIRATION. Aerobic respiration: Processes: Glycolysis, Krebs cycle, electron transfer chain. Products: H2O, CO2. Electron carriers: NAD+ and FAD. Location: Cytosol and mitochondria. Energy yield per glucose molecule: 30–32 ATP. Anaerobic respiration: Processes: Glycolysis. Products: CO2 and ethanol or lactate. Electron carriers: NAD+. Location: Cytosol. Energy yield per glucose molecule: 2 ATP.
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