Exercises: Energy yield

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

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

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

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.

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.

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.

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.

Under standard biochemical conditions ($\text{pH} = 7.0$, $25\ ^\circ\text{C}$), the complete combustion of $1\ \text{mol}$ of glucose yields $\Delta G^{\circ\prime} = -2870\ \text{kJ/mol}$ and the hydrolysis of $1\ \text{mol}$ of ATP yields $\Delta G^{\circ\prime} = -30.5\ \text{kJ/mol}$. However, in the cytoplasm of a living hepatocyte, the actual concentrations of ATP, ADP, and $\text{P}_\text{i}$ mean that the phosphorylation of ADP requires around $+50.0\ \text{kJ/mol}$, with roughly $30\ \text{mol of ATP}$ net per mole of oxidized glucose obtained experimentally.

1. a) Calculate and compare the theoretical percentage energy efficiency under standard conditions (assuming $36\ \text{ATP/glucose}$) versus the actual intracellular thermodynamic efficiency. Justify the fate of the fraction of free energy that is not stored in the phosphate bonds of ATP and its significance for homeothermic animals.
2. b) 2.4-Dinitrophenol (DNP) is a lipophilic molecule capable of transporting protons across the inner mitochondrial membrane, dissipating the electrochemical gradient. Predict, with reasoning, how treatment with DNP will affect the net yield of ATP per glucose, the rate of $\text{O}_2$ consumption by the cell, and the body temperature of the organism.

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.