The use of 'biochemical equations'

A panel on biochemical thermodynamics, sponsored by JCBN and convened by Robert A. Alberty, has produced a series of recommendations for nomenclature and tables in biochemical thermodynamics [34] (see also [35-38]). This report emphasizes the distinction between 'chemical equations', in which the full ionic states of all reacting species should be given in a balanced equation, and 'biochemical equations'. The full charges are often omitted from the equations used in routine biochemical presentations. For example an equation of the form

is commonly used in biochemistry. It makes no attempt to show the full ionization or complexation states or the reactants or to balance charges. It has the advantage that it is written in terms of sums of species and leads directly to the expression for the apparent equilibrium constant K'

which is a function of pH and magnesium ion concentration, as well as T, P and ionic strength. In the above biochemical equation, ATP, ADP and acetyl phosphate are obviously sums of species and, if K' is determined at low pH values, acetate represents the sum of the anion and undissociated acetic acid.

Similarly, it has become common to use NAD⁺ and NADH in equations, although both of these are in fact negatively charged at normal physiological pH values, without any attempt to balance charges and hydrogen atoms on other species in the equation. This may make it hard to tell whether a chemical equation or a biochemical equation is intended. In view of such difficulties, the panel has recommended that all indications of charges be removed from biochemical equations and that the full chemical equations, which are written in terms of individual species which may be charged (e.g. H⁺, Mg²⁺, RCOO^-, etc.) should be used for those specific cases where thermodynamic behaviour is to be considered.

In writing biochemical equations, it is necessary to use symbols that suggest sums of species and avoid symbols for only one of the species that may be present. Since both chemical equations and biochemical equations are needed in biochemistry it is important that the reader should be able to distinguish between these two types of equations at a glance. Failure to make such a clear distinction can lead to hybrid equations that do not have corresponding equilibrium constant expressions and have incorrect stoichiometry. For example, the hydrolysis of 1 mol of ATP to ADP at approximately pH 7 does not produce 1 mol of H⁺, as suggested by the equation

but about 0.6 mol. Thus it is recommended that hybrid equations, in which some charges but not others are given, should be avoided as misleading.

If these recommendations were to be implemented, the following paragraph would have to be added to Note (1) on page 23 of Enzyme nomenclature 1992 [14]:

"Since the equations representing the reactions are biochemical equations, they provide the basis for writing the expression for the apparent equilibrium constant K' at specified T, P, pH, pX and ionic strength. Here pX = -log[X] where X is any metal ion that is bound by the reactants. Biochemical equations do not balance hydrogen atoms, atoms of the bound metal or charge, but they do balance other kinds of atoms. The expression for the apparent equilibrium constant K' for any reaction can be written by looking at the biochemical equation. Chemical equations that do balance hydrogen ions, bound metal ions and charge can be written for these reactions and their equilibrium-constant expressions yield the equilibrium constant K, which is independent of pH and concentrations of free metal ions. Chemical equations have their uses in understanding how biochemical equations work and in analyzing the effects of pH and concentrations of free metal ions on the apparent equilibrium constants. In general, chemical equations are not unique because various choices can be made for the specific species used in writing a chemical equation."

Some of the changes in usage for biochemical equations that would be necessary if these recommendations were to be adopted are summarized below:

1. No biochemical equation should contain H⁺. If the number of protons produced or consumed in a reaction at pH 7 is of special interest, e.g. as it may be for nitrogenase, a comment to this effect may be added.

2. NAD(P) and NAD(P)H₂ should replace NAD(P)⁺ and NAD(P)H + H⁺. The alternative symbols NAD_ox and NAD_red were recommended but these have the disadvantage of not showing that the oxidation/reduction reaction is a two-electron change, for example in the reaction:

If it is necessary to indicate an oxidation/reduction reaction where the acceptor/donor is unknown, reduced acceptor/oxidized acceptor (or Acceptor_red/Acceptor_ox) should be used. Alternatively 2e may be used to represent a reactant in a two-electron transfer.

3. When CO₂ is produced, CO₂ can be used in writing biochemical equations if it is understood that it is produced in the gas phase. Otherwise carbonate should be used to represent the sum of the species CO₂, H₂CO₃, HCO₃^-, and CO₃^- in the solution. The term TotCO₂ may be used as an alternative to make this clearer.

4. Ammonia should replace NH₃ or NH₄⁺ in describing the sum of NH₄⁺ and dissolved NH₃ + H₂O = NH₄OH.

5. Cyanide should replace CN^- or HCN (e.g. in EC 4.4.1.9) as it represents the sum of both these species.

6. Nitrite and nitrate should replace NO₂^- and NO₃^-, respectively.

7. Ascorbic acid (D-erythro-ascorbic acid) should be replaced by ascorbate (D-erythro-ascorbate) to represent the sum of species.

8. Fe(II) should be used in place of Fe²⁺ to represent the sum of various complexed species of the ferrous ion.

The implementation of such recommendations would have substantial implications for the way we have become accustomed to present equations in biochemistry. The views of readers on the desirability of these proposals are being sought.

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