Introduction: Endergonic reactions require energy input in order to proceed (see GIBB'S FREE ENERGY). Almost every time a cell performs an endergonic reaction, such as linking amino acids, synthesizing small molecules, or cellular movement, it derives the needed energy from the splitting of ATP. Aerobic organisms produce most of their ATP through respiration, a complex set of reactions that transfer electrons from glucose to oxygen. Glycolysis is the first step in glucose metabolism. The success of glycolysis lies in its ability to couple energy releasing reactions to the endergonic synethesis of ATP.

Importance: Because ATP is considered the universal currency of biological energy, it is important to learn how cells make ATP. Also, properties of cells and chemical reactions affect the efficiency of ATP production.

Question: How can we determine the efficiency of ATP production?

Methods: The predominant source of energy in animal cells is the sugar glucose. The reaction of glucose with oxygen under standard conditions can be described by the following chemical equation:

C₆H₁₂O₆ + 6O₂ --> 6CO₂ + 6H₂O

When 1 mol (180 g) of glucose reacts with oxygen under standard conditions, 686 kcal of energy is released (DG⁰' = -686kcal/mol). If glucose is simply burned in air, all of this energy is released as heat. In the cell, however, this reaction is coupled to the synthesis of ATP from ADP in the following reaction:

C₆H₁₂O₆ + 6O₂ + 36Phosphate + 36ADP --> 6CO₂ + 6H₂O + 36ATP

In other words, the energy released when glucose reacts with oxygen is coupled with an endergonic reaction in order to produce ATP. However, only a fraction of the released energy goes into the high-energy bonds of ATP. Since the overall reaction is exergonic, some energy is lost as heat.

We can determine the efficiency of ATP production by comparing the energy in ATP created by the reaction to the energy released by the reaction:

where N is the number of ATP molecules formed and E_react is the energy released as heat in the chemical reaction that is coupled with the reaction to form ATP. E_ATP is the energy in one high energy phophoanhydride bond in ATP, or the free energy when ATP reacts to form ADP and phosphate (ATP à ADP + phosphate).

Under standard conditions, E_react = -686 kcal/mol and E_ATP = -7.3 kcal/mol. From the chemical reaction for the formation of ATP, we see that 36 molecules are formed. Therefore we calculate the efficiency as

In other words, only about 38.3% of the energy released from the reaction of glucose with oxygen is captured in ATP bonds.

Interpretation: An ATP efficiency of 38.3% is calculated under standard conditions (temperature is 298 Kelvin, pressure is 1 atm, pH is 7.0, and initial concentrations of reactants and products are equal). An E_ATP of -7.3 kcal/mol requires ATP, ADP, and phosphate to be present at equal concentrations.

In cells, however the concentration of ATP is often 5 to 10 times that of ADP. As a result, the free energy of ATP hydrolysis is about -12 kcal/mol. In cells, the efficiency of energy extraction from glucose is approximately 50%. As a comparison, the efficiency of an electric motor or gasoline engine is about 10% to 20%.

Conclusions: By examining the chemical reaction of glycolysis, we can determine the efficiency of ATP production in cells. Properties of cells, particularly the high ratio of ATP to ADP, contribute to the efficiency of ATP production under cellular conditions. Respiration is a successful process because the capture of energy into ATP bonds is relatively efficient.

1. Look at the equation from GIBB'S FREE ENERGY for calculating DG when the ratio of reactants to products does not equal 1:

where T is temperature in Kelvin, R is the universal gas constant (1.987 cal/molK), and C gives the concentration of products and reactants, respectively.

The free energy from the hydrolysis of ATP (ATP à ADP + phospate), under standard conditions, is DG⁰' = -7.3 kcal/mol. Assume the temperature in a particular cell is 320 K, the concentration of ATP is 0.4mg/mL, the concentration of ADP is 0.04 mg/mL, and the concentration of phosphate is 0.02 mg/mL. Calculate the new DG for ATP hydrolysis in this cell.

2. For the cell in question 1, what would the efficiency of ATP production be (assuming the free energy of the glucose reaction is still -686 kcal/mol)?

3. Oxidative phosphorylation is a step in respiration that allows for the synthesis of approximately 2.5 moles of ATP. The free energy for oxidative phosphorylation has a DG = -53 kcal/mol. What is the efficiency of ATP production from oxidative phosphorylation (assume cellular E_ATP = -12 kcal/mol)?

Sources: Darnell, J., H. Lodish, and D. Baltimore. 1986. Molecular Cell Biology. Scientific American Books, Inc., New York

Tobin, A. J. and R. E. Morel. 1997. Asking About Cells. Harcourt Brace & Company, New York.

Copyright 1999 M. Beals, L. Gross, S. Harrell