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Metabolism · Cellular metabolism

Energy yield

After studying glycolysis, the citric acid cycle (Krebs cycle), the electron transport chain and fermentation separately, it is time to do the math. Picture a soccer player sprinting down the field at the end of a match: how much ATP is actually obtained from one glucose molecule, and why is respiring so much more worthwhile than fermenting?

The complete balance of aerobic respiration

Per glucose molecule, in a eukaryotic cell, we count each stage separately.

Stage Net direct ATP NADH FADH₂
Glycolysis, cytosol 2 2 0
Pyruvate oxidation (two pyruvates to acetyl-CoA), matrix 0 2 0
Two turns of the citric acid cycle, matrix 2 equivalents (GTP/ATP) 6 2
Aerobic respiration in the eukaryotic cell: glucose is broken down in the cytosol to pyruvate, enters the citric acid cycle in the mitochondrial matrix, and the NADH and FADH₂ pass electrons to the transport chain and to the ATP synthase of the cristae; 4 direct ATP and 26–28 oxidative ATP are added, about 30–32 ATP in total Cytosol Glucose Glycolysis +2 ATP 2 pyruvate Matrix acetyl-CoA Krebs +2 ATP 10 NADH 2 FADH₂ Transport chain ATP synthase Direct ATP 4 + Chain and ATP synthase 26–28 ATP = Approximate total 30–32 ATP
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How many net ATP molecules are obtained in glycolysis per glucose molecule, and how many in total (classic theoretical figure) when completely respired aerobically?

How many net ATP molecules are obtained in glycolysis per glucose molecule, and how many in total (classic theoretical figure) when completely respired aerobically?

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State how many ATP molecules are obtained, according to currently accepted values, for each NADH and for each $\text{FADH}2$ that deliver their electrons to the electron…

State how many ATP molecules are obtained, according to currently accepted values, for each NADH and for each $\text{FADH}_2$ that deliver their electrons to the electron transport chain.

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In aerobic respiration, about $36$-$38\ \text{ATP}$ are obtained per glucose, of which only $2$ come from glycolysis. Calculate what percentage of the total yield is…

In aerobic respiration, about $36$-$38\ \text{ATP}$ are obtained per glucose, of which only $2$ come from glycolysis. Calculate what percentage of the total yield is contributed by the mitochondrial stages (taking $36\ \text{ATP}$ as the total) and comment on the result.

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A person ingests $100\ \text{g}$ of glucose in a meal (molar mass $180\ \text{g/mol}$, that is, about $0.56\ \text{mol}$). Calculate how many moles of ATP their body can…

A person ingests $100\ \text{g}$ of glucose in a meal (molar mass $180\ \text{g/mol}$, that is, about $0.56\ \text{mol}$). Calculate how many moles of ATP their body can obtain aerobically ($36\ \text{ATP}$ per glucose) and how many grams of ATP they are equivalent to (molar mass of ATP, $507\ \text{g/mol}$). Comment on the figure obtained.

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Respiration versus fermentation

Aerobic respiration oxidizes glucose completely and yields approximately 30–32 ATP per molecule in the model above. Fermentation regenerates NAD⁺ to keep glycolysis going: overall it yields 2 net ATP per glucose, which come from glycolysis, not from the conversion of pyruvate into lactate or ethanol.

Comparative diagram: glucose goes through glycolysis (2 ATP) and the pyruvate continues to the mitochondrion with oxygen (respiration, about 30–32 ATP in total) or is fermented to lactate or ethanol without oxygen (2 ATP in total), regenerating NAD⁺ for glycolysis; bars of ATP per glucose. Cytosol Glucose Glycolysis +2 ATP Pyruvate with O₂ Mitochondrion CO₂ + H₂O without O₂ Lactate or ethanol NADH → NAD⁺ regenerates NAD⁺ ATP per glucose Respiration ~30–32 ATP Fermentation 2 ATP
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Why is fermentation much less energy-efficient than aerobic respiration, even though both begin with glycolysis? Explain what happens to pyruvate in each case.

Why is fermentation much less energy-efficient than aerobic respiration, even though both begin with glycolysis? Explain what happens to pyruvate in each case.

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Rank from highest to lowest energy yield per glucose molecule: aerobic respiration, lactic acid fermentation, and alcoholic fermentation. Justify the ranking.

Rank from highest to lowest energy yield per glucose molecule: aerobic respiration, lactic acid fermentation, and alcoholic fermentation. Justify the ranking.

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Why can organisms that respire aerobically maintain larger and more active bodies than those that only ferment? Relate your answer to the energy yield of each pathway.

Why can organisms that respire aerobically maintain larger and more active bodies than those that only ferment? Relate your answer to the energy yield of each pathway.

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Calculate how many glucose molecules a cell needs to break down to obtain $180\ \text{ATP}$ aerobically ($36\ \text{ATP/glucosa}$) and how many by fermentation (…

Calculate how many glucose molecules a cell needs to break down to obtain $180\ \text{ATP}$ aerobically ($36\ \text{ATP/glucosa}$) and how many by fermentation ($2\ \text{ATP/glucosa}$). Comment on the implication of this difference for anaerobic organisms.

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In alcoholic fermentation, $2\ \text{mol}$ of ATP are obtained per mole of glucose. Calculate how many moles of glucose would need to be fermented to equal the ATP…

In alcoholic fermentation, $2\ \text{mol}$ of ATP are obtained per mole of glucose. Calculate how many moles of glucose would need to be fermented to equal the ATP obtained by respiring a single mole of glucose, and explain what problem this poses for an anaerobic microorganism in a sugar-poor medium.

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During a maximum speed $100\ \text{m}$ sprint, fast-twitch muscle fibers demand ATP at a rate of approximately $3.5\ \text{mmol}/(\text{kg}\times\text{s})$. In those…

During a maximum speed $100\ \text{m}$ sprint, fast-twitch muscle fibers demand ATP at a rate of approximately $3.5\ \text{mmol}/(\text{kg}\times\text{s})$. In those same fibers, mitochondrial oxidative phosphorylation has a maximum production rate of barely $0.4\ \text{mmol}/(\text{kg}\times\text{s})$, whereas homolactic fermentation can generate up to $4.0\ \text{mmol}/(\text{kg}\times\text{s})$.

  1. a) Based on these kinetic data, justify why it is energetically profitable for the muscle cell to massively activate lactic fermentation even though its stoichiometric yield per mole of glucose is about 16-18 times lower than that of aerobic respiration.
  2. b) Predict what immediate metabolic and intracellular consequences (in relation to pH, substrate availability, and the activity of enzymes such as phosphofructokinase-1) would occur if an attempt were made to sustain this fermentative rate for several minutes, explaining why muscle fatigue develops.
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In a laboratory chemostat, a mixed microbial community composed of two species with identical affinity for glucose is cultured: a yeast with facultative aerobic…

In a laboratory chemostat, a mixed microbial community composed of two species with identical affinity for glucose is cultured: a yeast with facultative aerobic respiration and a strict fermentative bacterium (obligate anaerobe).

  1. a) If the bioreactor, initially kept without oxygen, begins to be continuously oxygenated while maintaining a constant supply of glucose, predict the evolution of the biomass of both populations and the change in specific glucose consumption per cell (Pasteur effect). Justify your prediction by relating the energy efficiency of both catabolic pathways to macromolecule synthesis.
  2. b) A student argues that, since aerobic respiration is thermodynamically more efficient, fermentation is a primitive biological pathway destined to disappear through natural selection. Refute this statement by proposing two current physiological situations or ecological niches where fermentation constitutes the optimal or irreplaceable metabolic strategy, justifying why in each case.
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The graph compares the ATP molecules obtained per glucose molecule according to the metabolic pathway used. A yeast culture without oxygen degrades $100\ \text{mol}$ of…

The graph compares the ATP molecules obtained per glucose molecule according to the metabolic pathway used. A yeast culture without oxygen degrades $100\ \text{mol}$ of glucose by alcoholic fermentation. Calculate, from the graph, how many moles of ATP it obtains, how many it would obtain if it respired that same glucose aerobically, and how many times more efficient the aerobic pathway is.

10 20 30 ATP 2 2 36 glycolysis fermentation respiration
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Real yield and its losses

During a hot football practice in August, players sweat and give off a large amount of body heat: how much of the energy in glucose does a cell really use to synthesize ATP, and why is the rest dissipated? (Answer below.)

Bar chart illustrating the approximate split of the fuel's chemical energy between useful ATP and dissipated heat illustrative split, not a fixed proportion useful ATP(~40%) heat(~60%) part of the heat comes from H⁺ leaks across the mitochondrial membrane
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What does it mean that a metabolic pathway has an energy yield of $40\ \%$? Explain what happens to the rest of the energy contained in the food.

What does it mean that a metabolic pathway has an energy yield of $40\ \%$? Explain what happens to the rest of the energy contained in the food.

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The energy of foods is usually expressed in kilocalories. Explain what a kilocalorie is and what relationship it has with the energy that the cell finally stores in the…

The energy of foods is usually expressed in kilocalories. Explain what a kilocalorie is and what relationship it has with the energy that the cell finally stores in the form of ATP.

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The classic theoretical balance of cellular respiration predicts the synthesis of $36$ to $38\ \text{ATP}$ per glucose molecule, but in vivo measurements in mammalian…

The classic theoretical balance of cellular respiration predicts the synthesis of $36$ to $38\ \text{ATP}$ per glucose molecule, but in vivo measurements in mammalian mitochondria show that the actual yield rarely exceeds $30$-$32\ \text{ATP}$.

  1. a) Justify at a molecular and thermodynamic level two physiological causes that explain this discrepancy, referring to the use and dissipation of the electrochemical proton gradient between the intermembrane space and the mitochondrial matrix.
  2. b) The brown adipose tissue of hibernating mammals and newborns expresses the uncoupling protein thermogenin (UCP-1) in its inner mitochondrial membrane. Apply Mitchell's chemiosmotic hypothesis to explain how UCP-1 alters the ratio of $\text{ATP/O}_2$ consumed, and deduce what adaptive advantage it provides against cold thermal stress.
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Energy per gram of fuel

Comparative diagram of the energy content per gram and the storage capacity of carbohydrates versus lipids. kcal/g 4 glucose 9 fat

Even lying still, your body spends ATP on Na⁺/K⁺ pumps, protein synthesis and heartbeat and breathing muscles. Endotherms like mice and humans also burn fuel to stay warm, so their oxygen use rises when it gets cold. Ectotherms like lizards do not, so their oxygen use falls as the temperature drops.

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The human body spends energy even at absolute rest (basal metabolism). Name two processes that consume ATP even when we are lying down and still, and explain why they…

The human body spends energy even at absolute rest (basal metabolism). Name two processes that consume ATP even when we are lying down and still, and explain why they are essential to staying alive.

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The combustion of $1\ \text{g}$ of glucose releases about $4\ \text{kcal}$ and that of $1\ \text{g}$ of fat about $9\ \text{kcal}$. Explain what that difference is due…

The combustion of $1\ \text{g}$ of glucose releases about $4\ \text{kcal}$ and that of $1\ \text{g}$ of fat about $9\ \text{kcal}$. Explain what that difference is due to and calculate how many grams of fat provide the same energy as $90\ \text{g}$ of glucose.

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During a marathon, a runner performs about $10000\ \text{kJ}$ of useful work. If their body has an overall efficiency of $25\ \%$, calculate how much chemical energy…

During a marathon, a runner performs about $10000\ \text{kJ}$ of useful work. If their body has an overall efficiency of $25\ \%$, calculate how much chemical energy from food they have had to mobilize and explain why their body heats up so much during the race.

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The adult human brain has a mass of about $1400\ \text{g}$ (around $2\ \%$ of body mass), but at rest it consumes $20\ \%$ of the oxygen and glucose of the entire body,…

The adult human brain has a mass of about $1400\ \text{g}$ (around $2\ \%$ of body mass), but at rest it consumes $20\ \%$ of the oxygen and glucose of the entire body, degrading approximately $120\ \text{g}$ of glucose per day (molar mass $= 180\ \text{g/mol}$).

  1. a) Justify at a molecular and membrane transport level which continuous physiological processes of neurons explain such a basal expenditure of ATP at rest.
  2. b) Calculate the daily moles of ATP produced by the brain assuming a net yield of $30\ \text{mol of ATP}$ per mole of oxidized glucose. If the total intracellular reserve of ATP in brain tissue is $2.5\ \mu\text{mol/g}$, calculate how many seconds of activity this reserve would last if oxidative phosphorylation were stopped instantaneously.
  3. c) Based on the results of b), justify why cerebral ischemia causes loss of consciousness in less than $10\ \text{seconds}$, and explain why the brain cannot sustain its energy viability through fermentation from endogenous glycogen, unlike skeletal muscle fibers.
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An ecophysiology lab compares the metabolic expenditure of a homeothermic mammal (a $25\ \text{g}$ mouse) and a poikilothermic reptile (a $25\ \text{g}$ lizard) by…

An ecophysiology lab compares the metabolic expenditure of a homeothermic mammal (a $25\ \text{g}$ mouse) and a poikilothermic reptile (a $25\ \text{g}$ lizard) by measuring $\text{O}_2$ consumption (in $\text{mL}\ \text{O}_2\times\text{g}^{-1}\times\text{h}^{-1}$) at different ambient temperatures.

  1. a) Predict how the consumption of $\text{O}_2$ will vary in each animal when the ambient temperature drops sharply from $22\ \text{°C}$ to $6\ \text{°C}$. Justify your answer by relating cellular respiration to the maintenance of body temperature in homeotherms.
  2. b) In a situation of extreme food shortage for several weeks, the lizard survives by remaining inactive, while the mouse dies within 24 to 48 hours if its reserves are depleted. Justify this fact based on the basal metabolic rate and the fate of ATP in both animals.
  3. c) In cold environments, mammals activate thermogenesis in brown adipose tissue via the uncoupling protein thermogenin (UCP-1) in the inner mitochondrial membrane. Explain how this protein alters oxidative phosphorylation to dissipate energy as heat without ATP synthesis.
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Summary

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