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5th Year OL · Biology
Metabolism · Cellular metabolism

Cellular respiration

Before a Gaelic football match in Croke Park, a player's cells must keep releasing energy from glucose for 70 minutes. A cell can obtain energy from glucose in two ways: by burning it all at once, as in a laboratory, or by breaking it down little by little, in dozens of linked steps, capturing the energy as ATP at each one. The second option is cellular respiration, and it is the one used by almost all living things.

Overview: the equation and the four stages

The four stages of aerobic respiration in order: glycolysis in the cytosol, then link reaction, citric acid cycle and electron transport chain in the mitochondrion. 1 Glycolysis cytosol 2 Link reaction matrix 3 Citric acid cycle: matrix 4 Electron chain inner membrane
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Name the four stages of aerobic respiration and state where in the eukaryotic cell each one takes place.

Name the four stages of aerobic respiration and state where in the eukaryotic cell each one takes place.

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In the diagram of aerobic respiration, state which stage corresponds to each numbered box (1, 2, and 3), name the molecules labelled A and B, and indicate where in the…

In the diagram of aerobic respiration, state which stage corresponds to each numbered box (1, 2, and 3), name the molecules labelled A and B, and indicate where in the cell each stage takes place.

glucose 1 2 3 A CO₂ O₂ B ATP
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Glycolysis: the first step, in the cytosol

If you grow yeast (as used in brewing) or muscle cells in a container with no oxygen at all and with glucose, you find that the sugar is used up quickly and the cells survive by producing ATP: how does the cell manage to extract energy from a carbohydrate without using oxygen?

Diagram of the two phases of glycolysis, with the initial expenditure of two ATP and the final production of four ATP, two NADH and two pyruvate molecules from one glucose. glucose (6C) glycolysis phase 1: invests 2 ATP phase 2: produces 4 ATP and 2 NADH pyruvate pyruvate
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Where in the cell does glycolysis occur, and what net products are obtained from one molecule of glucose in this stage?

Where in the cell does glycolysis occur, and what net products are obtained from one molecule of glucose in this stage?

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For each glucose molecule, glycolysis has a net balance of $2\ \text{ATP}$ and $2$ NADH. Explain why it is called a 'net' balance, detailing how many ATP are consumed in…

For each glucose molecule, glycolysis has a net balance of $2\ \text{ATP}$ and $2$ NADH. Explain why it is called a 'net' balance, detailing how many ATP are consumed in the first phase and how many are produced in the second.

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The fate of pyruvate: respire or ferment

Diagram of the fate of pyruvate: with oxygen it enters the mitochondrion (aerobic respiration); without oxygen it is fermented in the cytosol and lactate or ethanol is obtained. pyruvate with O₂ mitochondrion aerobic respiration without O₂ fermentation in the cytosol lactate or ethanol

Fermentation and the Pasteur effect

The Pasteur effect: when oxygen is present, yeast and muscle cells switch from fermentation to aerobic respiration. Respiration gives about 30 ATP per glucose instead of 2, so the cell needs far less glucose (about one-fifteenth) for the same ATP supply, and glucose consumption falls.

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What is pyruvate and what are its two main fates after glycolysis depending on whether oxygen is available or not? State what type of metabolic pathway it follows in…

What is pyruvate and what are its two main fates after glycolysis depending on whether oxygen is available or not? State what type of metabolic pathway it follows in each case.

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Define fermentation and name the two main types with their final products, indicating an organism or tissue that carries out each one.

Define fermentation and name the two main types with their final products, indicating an organism or tissue that carries out each one.

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In lactic acid fermentation, pyruvate is converted into lactate. Explain why this process allows $\text{NAD}^+$ to be regenerated and in what situations human muscles…

In lactic acid fermentation, pyruvate is converted into lactate. Explain why this process allows $\text{NAD}^+$ to be regenerated and in what situations human muscles use it.

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Yeasts and our muscle cells can respire or ferment depending on the available oxygen. Explain how the cell 'decides' between one pathway and the other (the Pasteur…

Yeasts and our muscle cells can respire or ferment depending on the available oxygen. Explain how the cell 'decides' between one pathway and the other (the Pasteur effect) and what advantage it obtains when, oxygen being present, it reduces glucose consumption while maintaining the same ATP supply.

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The citric acid cycle (Krebs cycle): in the mitochondrial matrix

When mitochondria are supplied with glucose labelled with radioactive carbon, the $\text{CO}_2$ they give off contains that label, but the amount of oxaloacetate in the matrix stays constant after millions of molecules have been broken down: how can the fuel be completely oxidised within a pathway whose components never run out?

Krebs cycle in the mitochondrial matrix: acetyl-CoA enters, two CO₂ leave, NADH, FADH₂ and ATP are produced, and oxaloacetate is regenerated to start another turn. acetyl-CoA enters CO₂ leaves (×2) NADH, FADH₂, ATP oxaloacetate regenerated Krebs cycle mitochondrial matrix

The mitochondrion and its origin

A mitochondrion has a smooth outer membrane, a folded inner membrane (the folds are cristae, where the electron transport chain and ATP synthase sit) and the matrix inside (link reaction and citric acid cycle). Mitochondria have their own circular DNA, ribosomes and divide by binary fission. This supports the endosymbiotic theory: they descend from aerobic bacteria engulfed by an ancestral cell. Early Earth's atmosphere had almost no oxygen, so the first cells relied on glycolysis and fermentation; oxygen-using chains evolved later.

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Mitochondria possess their own DNA, their own ribosomes and divide by binary fission. Explain what evolutionary origin these data suggest (the endosymbiotic theory) and…

Mitochondria possess their own DNA, their own ribosomes and divide by binary fission. Explain what evolutionary origin these data suggest (the endosymbiotic theory) and why these organelles are the right place to house cellular respiration.

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In a class debate on cellular origins, a student claims: "The enzymes of glycolysis and those of the mitochondrial electron transport chain must have evolved at the same…

In a class debate on cellular origins, a student claims: "The enzymes of glycolysis and those of the mitochondrial electron transport chain must have evolved at the same time in the first living cells to prevent cytosolic $\text{NAD}^+$ from being depleted."

  1. a) Refute the student's statement by providing two geochemical arguments about the conditions of early Earth's atmosphere and one evolutionary argument based on the endosymbiotic theory.
  2. b) If the first organisms had neither oxygen nor complex membrane-dependent electron transport systems, biochemically justify the unavoidable need to couple glycolysis to fermentation reactions for the continuity of cellular life.
  3. c) Predict what would happen to an obligate anaerobic bacterium, whose only route for regenerating $\text{NAD}^+$ is lactic fermentation, if a mutation inactivated its lactate dehydrogenase in a medium where glucose is its only carbon and energy source.
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The respiratory chain and oxidative phosphorylation

Animation of the respiratory chain: an electron travels from NADH through complexes I, III and IV to oxygen; at each complex a proton H⁺ is raised into the intermembrane space, and then all three return to the matrix through ATP synthase, which spins. inner membrane I III IV ATP synthase NADH → e⁻ O₂ + 4H⁺ → 2H₂O pumping of H⁺ H⁺ returns → ATP

Poisons and uncouplers: when the chain fails

Inner mitochondrial membrane with the respiratory chain and ATP synthase in two cases: A, cyanide binds to complex IV, electrons do not reach oxygen and no ATP is formed; B, the uncoupler DNP returns protons to the matrix without passing through ATP synthase and the energy is lost as heat. A. Cyanide: blocks complex IV Qc IIIIIV NADH → NAD⁺e⁻ ATP synthase intermembranespaceinnermembranematrix ½ O₂ H₂O CN⁻ With no final acceptor, the complexes do not pump H⁺: there is no gradientand ATP synthase stops → no ATP is formed even if O₂ is present. B. DNP (uncoupler): H⁺ leak without ATP Qc IIIIIV NADH → NAD⁺e⁻ ATP synthase intermembranespaceinnermembranematrix ½ O₂ H₂O H⁺H⁺H⁺ H⁺H⁺H⁺H⁺H⁺ H⁺ heat DNP The H⁺ return to the matrix without passing through ATP synthase:O₂ is consumed, but the energy of the gradient is lost as heat.

Carbon monoxide (for example from a faulty boiler) binds haemoglobin more strongly than oxygen, so less O₂ reaches the tissues; the chain starves of its final acceptor and cells shift to fermentation. Cyanide instead blocks complex IV inside the mitochondrion itself.

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Carbon monoxide binds to haemoglobin with more affinity than oxygen. a) Explain what effect it has on the transport of $\text{O}2$ to the tissues. b) Reason which stages…

Carbon monoxide binds to haemoglobin with more affinity than oxygen. a) Explain what effect it has on the transport of $\text{O}_2$ to the tissues. b) Reason which stages of cellular respiration will be affected and why cells switch to fermentation even when they have glucose. c) Compare the toxicity mechanism of carbon monoxide with that of cyanide.

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Back to the beginning: By breaking glucose down step by step instead of burning it all at once, the cell avoids an uncontrolled combustion that would destroy its structures and manages to convert more than $30\,\%$ of that chemical energy into 30-32 ATP bonds that can be used directly.

Summary

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