Bioenergetics

Prof. Mamoun AhramSummer semester, 2021

Energy and reactions

Every molecule has a potential energy stored in it and it is called Gibbs free energy (or G).

The maximum amount of useful energy that can be obtained from a reaction is called ΔG, which is the change in Gibbs free energy between products and substrates.

Accordingly, reactions can be exergonic or endergonic.

The value of ∆G0’ tells you whether the reaction

requires or releases energy and the amount of

energy involved, the ratio of

products:substrates, and if it is favorable to the

cell to happen.

If ΔG0 < 0, the reaction proceeds towards

the formation of products

If ΔG0 > 0, the reaction proceed towards

formation of reactants.

Important notes about enzymatic reactions

1. Enzymes do not reduce ∆G0’ of reactions.

2. A spontaneous reaction is not really “spontaneous”: ∆G0’ is not an indicator of the

velocity of the reaction or of the rate at which equilibrium can be reached. In the cell, they

depend on the efficiency and amount of enzyme available.

Energy and metabolic pathways

Anabolic Pathways (Endergonic reactions):

Reactions consume energy to build biomolecules (Protein, Glycogen & lipids)

Catabolic Pathways (Exergonic reactions):

Reactions release energy by breaking down larger molecules into simpler ones(example: glycolysis)

Metabolism is a linked series of chemical reactions (biochemical pathways)

The first law of thermodynamics: energy is conserved.

The different ΔG’s of reactions

∆G0’ = ∆G with 1M concentration of reactants & products at standard conditions (25C & 1 atmospheric pressure, pH = 7)

∆G0 = standard free energy difference of a system with 1M concentration of reactants & products

∆G = the free energy difference of a system at any condition

The value of ΔG0′ tells you whether

the reaction requires or releases

energy, the amount of energy

involved, and the ratio of products to

substrates at equilibrium.

Chemical equilibrium is the state where

the rate of a forward reaction and its

reverse reaction are not changing (not

necessarily zero)

When ∆G = 0, the reaction is at equilibrium, meaning that the quantities

of reactants and products do not change, that is they do not become

different than at ∆G0’.

Problem 1

What is the ∆G0’ of the reverse reaction (glucose 1-P → glucose 6-P)?

How is ∆G calculated?

The value of ΔG for a reaction can be influenced by the initial concentrations of substrates and products

temperature

pH

pressure

• Note: If there are more A and B than C and D, then the value

(In Keq) becomes < 0, and ∆G becomes lower than ∆G0’.• An endergonic reaction may become exergonic.

• THINK: what would happen if you increase T or R?!!

Some math!

If (Keq > 1), then In Keq > 0

If (Keq < 1), then In Keq < 0

In = 2.303log10X

Questions

Consider this reaction that has a ∆G0’ = +0.4 kJ/mol.

A + B C + D

1M A, 1M B, 0.1M C and 0.1 M D are added to a container at room temperature. Which of the following statements is true?

A. The reaction will proceed in the forward direction to reach equilibrium

B. The reaction will proceed in the backward direction to reach equilibrium

C. The reaction will not proceed in either direction; it is already at equilibrium

D. Cannot be determined from the information provided

Something extra…what does G really mean?

G is amount of energy contained within a molecule.

G = H – TSH is enthalpy (the amount of energy within bonds of molecules)

T is the temperature that a system exists in (in Kelvin; 0C = 273 K)

S is entropy (disorder within a system)For example, H2O as ice has less entropy than H2O as liquid.

For reactions: ∆G = ∆H – T.∆STΔS is a correction for the amount of energy that has gone into an increase in the entropy (disorder in arrangement of molecules) of the system.

ΔH is the change in enthalpy of the reaction and is equivalent to the chemical bond energy of the products minus that of the reactants.

If ∆H > 1, the reaction is endothermic.

If ∆H < 1, the reaction is exothermic. The second law of thermodynamics: the universe tends toward disorder.

∆G’s of sequential reactions are additivesExample

How do cells make an endergonic reaction exergonic?

Strategy 1: The use of ATP (coupling reactions)

The bonds between the phosphate groups in ATP are called phosphoanhydride bonds, which when hydrolyzed, energy is released. Why?

The products of the reaction (ADP and phosphate) are more stable, with lower bond energies than the reactants (ATP and water [H2O]) and, therefore, ATP hydrolysis is energetically favorable and proceeds with release of energy as heat.

In the cell, ATP is not hydrolyzed directly, and energy is not released as heat from ATP hydrolysis and transferred efficiently into energy-requiring processes. Instead, cellular enzymes transfer the phosphate group to an intermediate that is part of the energy-requiring, phosphoryl transfer reaction.

Strategy 2: the use of activated intermediates

1. Hexokinase uses the energy in ATP to phosphorylate glucose forming glucose-6-phosphate.

2. Phosphoglucomutase isomerizes glucose-6-phosphate to glucose-1-phosphate.

3. (UDP)-glucose pyrophosphorylase cleaves a ~P bond in uridine triphosphate forming UDP-glucose, an activated intermediate, and release pyrophosphate.

4. A pyrophosphatase hydrolyzes the pyrophosphate to inorganic phosphate releasing additional energy.

5. Glycogen synthase uses the energy in the phosphoester bond of UDP-glucose to add the glucosyl unit to an existing glycogen.

Notes:

• ~P means a high-energy phosphate bond

• UTP is used for combining sugars, CTP in lipid synthesis, and GTP in protein synthesis

Other high-energy compounds

phosphoenolpyruvate + ADP + H+ → pyruvate + ATP: ΔGo’ = –7.4 kcal/mol

Strategy 3: Manipulating product/substrate ratio

The reaction has a small positive ΔG0′ for glucose 1-P

synthesis (+1.65 kcal/mol) and, at equilibrium, the ratio of [glucose 1-P]/[glucose 6-P] is approximately 6/94

If another reaction uses glucose 1-P, the ratio becomes 3/94, and ΔG becomes exergonic, a thermodynamically favorable reaction.

Can you calculate ΔG of G6P G1P reaction under the new ratio?

http://faculty.une.edu/com/courses/bionut/distbio/obj-512/Chap19-chapproblems.htm

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Strategy 4: the use of electron carriersOxidation of fuel such as glucose is the major source of ATP.

Energy is transferred from fuel molecules to electron carriers (i.e. NAD+ and FAD +), which transfer electrons to O2 through which an electrochemical gradient is created across the inner mitochondrial membrane, which is used to form ATP.

Oxidation and reduction must occur simultaneously.

Reduction potential

E0′ of a compound is a measure (in volts) of the energy change when that compound accepts electrons (becomes reduced).

E0′ can be considered an expression of the willingness of the compound to accept electrons.

Each oxidation–reduction reaction has a fixed amount of energy (ΔG0′), which is directly proportional to the ΔE0′ (the difference in reduction potentials of the oxidation–reduction pair).

ΔG°’ = -nFΔE°

where

n is the number of electrons transferred

F (Faraday constant) = 96.5 kJ/volt or 23.06

kcal/voltE = the reduction potential (volts)G = the free energy (Kcal or KJ)

Reduction potentials

Oxygen is the best electron acceptor with the largest positive reduction potential (i.e., is the most willing to accept electrons and be reduced).

The transfer of electrons from all compounds to O2 is energetically favorable and occurs with energy release.

Electrons move from compounds with lower reduction potential (more negative ) to compounds with higher reduction potential ( more positive).

Oxidation and reduction must occur simultaneously.

NADH versus FADH2

NADH FADH2

Thermogenesis

The first law of thermodynamics (no energy is lost).

Thermogenesis: production of heat as a consequence of oxidizing fuels and hydrolyzing ATP when performing work.

Shivering thermogenesis (ATP utilization): responding to sudden cold with asynchronous muscle contractions

Non-shivering thermogenesis: generation of heat without production of ATP

More fuel oxidation to produce ATP generating more heat.