Bioenergetics

Chapter 16

Bioenergetics

The properties of enzymes as catalysts for chemical reactions were considered in Chapter 6. This chapter now considers some of the associated energetic aspects of enzyme reactions in the cell.

Chemical equilibria

Considering the reaction:

< ?xml:namespace prefix = "mml" />A+BC+D

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if solutions of A and B are mixed and an appropriate enzyme is added C and D will be formed. Once this happens the back reaction will also take place with the re-conversion of C + D to A + B. Net production of C and D proceeds until the concentrations of substrates and products have adjusted to values where the rate of the back reaction is equal to the rate of the forward reaction. At this point, there will be no further net formation of products and the reaction is said to have attained equilibrium.

The relative concentrations of reactants and products for a particular reaction at equilibrium is characteristic of that reaction and is defined by the equilibrium constant (Keq). This is the product of the concentrations of products formed at equilibrium divided by the concentration of reactants remaining. Thus for the reaction given above:

Keq=[C]×[D][A]×[B]

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Reactions have widely differing values of Keq. Where Keq is very large, the reaction proceeds until virtually all the initial reactants have been converted to products. Such reactions are described as irreversible or effectively irreversible. Where Keq is very small, equilibrium is reached when only a small proportion of the initial reactants have been converted to products. Finally, for reactants with a value of Keq near to 1, the reactants and products are present in nearly equal proportions at equilibrium and the reaction will proceed in either direction depending on the initial concentration of products and reactants.

Biochemists find it useful to employ a thermodynamic function termed Gibbs free energy (abbreviated to free energy or the symbol G) in the consideration of enzyme reactions. For present purposes, the free energy of a system may be described as the potential of that system for doing work at constant temperature and pressure. The free energy of a system is not measurable, but the free energy changeG) which occurs during the conversion of substrate to products in an enzyme reaction can be quantified. The free energy change which occurs during a reaction is characteristic of that reaction if the reactants and products are initially present at standard concentrations. This standard free energy changeG0) is defined as the free energy change which occurs when both substrate(s) and products(s) are initially present at a concentration of 1 M, and 1 mol of reactant is converted to 1 mol of product.

The standard free energy change of a reaction is related to the equilibrium constant as follows:

ΔG°=RTlnKeq

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where R is the gas constant and T is the absolute temperature.

Many reactions involve the production or removal of hydrogen ions. For this reason it is convenient to redefine the standard state to be at pH 7 rather than at pH 0 (i.e. 1 M H+). The standard free energy change at pH 7 is written ΔG0 and is related to the equilibrium constant at pH 7 (Keq’) by the equation:

ΔG°=RTlnKeq

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Thus reactions with a high value of Keq’ have a large negative standard free energy change, while reactions with a low Keq’ have a large positive ΔG0’ For reactions with Keq’ near 1, the standard free energy change is near zero. Values of Keq’ together with the corresponding values of ΔG0′ are given in Table 16.1.

image 1·0 0

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Reactions will proceed only if the change in free energy, ΔG, is negative. The magnitude of the actual free energy change that occurs during a reaction is a function of the standard free energy change characteristic of that reaction and also of the initial concentrations of reactants and products:

ΔG=ΔG°+RTln[C]×[D][A]×[B]

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where [A], [B], [C] and [D] are the initial concentrations of reactants and products in the system. If the reactants and products are initially present at their equilibrium concentrations then the above equation reduces to ΔG = 0 and no energy can be obtained from the system.

For reactions with a large negative ΔG0’, ΔG will always be negative and hence the reaction always proceeds in the forward direction unless the initial concentration ratio of products to reactants is extremely high. Where ΔG0’ is near zero, the sign of ΔG will depend on the initial concentration of products and reactants and the reaction can be made to proceed in either direction by manipulation of these concentrations. If, however, ΔG0′ is large and positive, ΔG will also be positive and such a reaction will not proceed. It is, however, often possible to couple a reaction with a positive free energy change to another with a numerically larger negative free energy change. Since free energy changes are additive, the combined overall reaction will have a negative free energy change and will then proceed.

It should be recalled at this point that enzymes alter the rate at which a reaction occurs, but do not affect the position of equilibrium. Enzymes likewise have no effect on the free energy change of a reaction or on the direction in which a reaction will proceed.

ATP (adenosine triphosphate)

ATP occurs in all cells and is a universal intermediate in cell energy metabolism. The structure of ATP is shown below. The base adenine is joined to C-1′ of ribose, the 5′ position of which is linked to a phosphate residue to form adenosine monophosphate (AMP). Addition of a second

ΔG=ΔG°+RTln[C]×[D][A]×[B]

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phosphate group to the first via an anhydride bond gives the compound adenosine diphosphate (ADP) while ATP is derived by the addition of a further phosphate again via an anhydride linkage. At pH 7·4 ATP bears four negative charges and forms a stable complex with Mg2+ ions.

ATP can be hydrolysed enzymically to ADP and inorganic phosphate:

ATP4+H2OADP3+phosphate2+H+

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The standard free energy change (ΔG0’) of this reaction is approximately −30 kJ mol−1 and this is high relative to many other hydrolysis reactions (Table 16.2). The high standard free energy of hydrolysis of ATP arises in part from the fact that the products of the reaction, ADP and phosphate, both carry negative charges and hence tend to repel each other. Hydrolysis of the terminal phosphate–phosphate bond of ATP can be regarded as relieving some of the intramolecular strain caused by the presence of neighbouring negatively charged groups in the molecule.

Table 16.2

The standard free energy change (ΔG0’) of hydrolysis of some phosphate-containing compounds

Compound image
Phosphoenolpyruvate −53·5
1,3-Diphosphoglycerate −49·5
Phosphocreatine −44·0
ATP −29·4
Glucose 1-phosphate −21·0
Fructose 6-phosphate −16·0
Glucose 6-phosphate −13·8
3-Phosphoglycerate −13·0
Glycerol 1-phosphate −9·6

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ATP can also undergo hydrolysis as follows:

ATPAMP+pyrophosphate

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The value of ΔG0′ for this reaction is also −30 kJ mol−1 Where this reaction occurs, the pyrophosphate is rapidly hydrolysed to phosphate by the enzyme pyrophosphatase:

Pyrophosphate + H2O → 2 phosphate ΔG°’ = −30 kJ mol−1

The overall effect of the combined reactions is the hydrolysis of the two terminal phosphate–phosphate bonds of ATP with the formation of AMP and two phosphate molecules. The value of ΔG0′ for the overall reaction is then −60 kJ mol−1.

The other nucleoside triphosphates UTP, CTP and GTP are also involved in certain biosynthetic reactions. These triphosphates are regenerated by transfer of the terminal phosphate group from ATP by the following transferase reactions:

ATP+GDPADP+GTPATP+UDPADP+UTPATP+CDPADP+CTP

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The value of ΔG0′ is approximately zero, i.e. the values of ΔG0′ for hydrolysis for all the nucleoside triphosphates are similar so that the direction of the reaction depends on the relative concentrations of the reactants.

Since the hydrolysis of the terminal phosphate bond of ATP proceeds with a large negative standard free energy change, ATP is sometimes referred to as a high-energy compound, or, in older texts, as possessing high-energy bonds. It is important to realize that the function of ATP as an intermediate in energy metabolism depends on the fact that the value of ΔG for ATP hydrolysis at the concentrations of ATP, ADP and phosphate present in the cell, is large and negative, and this is the only sense in which the ‘high energy’ terminology should be understood. For example consider conditions under which ATP, ADP and phosphate are mixed at their equilibrium concentrations. Then the value of ΔG is zero and no energy could be obtained from the system, although ATP is still present.

The ATP/ADP cycle

In the cell, ATP can be regarded as undergoing a continuous cycle of breakdown and resynthesis:

ATP+GDPADP+GTPATP+UDPADP+UTPATP+CDPADP+CTP

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The free energy released by the hydrolysis of ATP is used to drive biosynthetic reactions and also to drive the active transport of metabolites across cell plasma membranes and the membranes of intracellular organelles. In some cells ATP is used for specialized purposes as in the case of muscle contraction. During these reactions ADP and phosphate are produced. In animal cells the ATP is resynthesized from ADP and phosphate by the process of oxidative phosphorylation which occurs in the mitochondria; this uses the free energy released by the oxidation of nutrients to drive the ATP hydrolysis reaction in reverse. Bacteria synthesize ATP by a similar process of oxidative phosphorylation. In plant cells the energy for ATP synthesis comes from the absorption of light and the process is termed photosynthetic phosphorylation. ATP turns over rapidly in the cell although the total pool of adenine nucleotides (ATP + ADP + AMP) remains relatively constant. ATP can thus be regarded as an intermediate in the transfer of free energy from substrate oxidation to energy-utilizing processes. It is able to fulfil this role because, while the ΔG for ATP hydrolysis in the cell is high enough to drive synthetic reactions, it is also low enough to allow the hydrolytic reaction to be reversed by the input of free energy from oxidative reactions.

A number of other phosphate-containing compounds have standard free energy changes of hydrolysis even greater than that of ATP (Table 16.2). Reactions in which such molecules transfer their terminal phosphate groups to ADP to form ATP are therefore energetically favourable. ATP can be formed in this way from ADP plus phosphoenolpyruvate (page 229), ADP plus creatine phosphate (page 331) and ADP plus 1,3-diphosphoglycerate (page 228). All these are important so-called substrate level phosphorylation reactions although far more ATP is synthesized by oxidative phosphorylation and the respiratory chain.

Utilization of ATP

Biosynthetic reactions

Degradative and hydrolytic reactions in general have a large negative value of ΔG0′. Consider for example the hydrolysis of the amino acid glutamine to glutamate and ammonium ions which is catalysed by the enzyme glutaminase:

Glutaminegluamate+NH4+

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ΔG0′ for this reaction is −14·3 kJ mol−1, i.e. the equilibrium position of the reaction lies far to the right. From the previous discussion, the value of AG for this reaction will be negative at physiological concentrations of glutamine and glutamate and the reaction will proceed in the direction of glutamine hydrolysis.

Under certain conditions it is necessary to synthesize glutamine from glutamate and ammonia. Free energy changes are additive, and glutamine is synthesized by using the free energy of ATP hydrolysis to reverse the glutamine hydrolysis reaction:

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Dec 10, 2015 | Posted by in General Dentistry | Comments Off on Bioenergetics
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