text: For some polyprotic acids, dissociation (or association) occurs at more than one nonequivalent site, and the observed macroscopic equilibrium constant, or macro-constant, is a combination of micro-constants involving distinct species. When one reactant forms two products in parallel, the macro-constant is a sum of two micro-constants,  This is true for example for the deprotonation of the amino acid cysteine, which exists in solution as a neutral zwitterion . The two micro-constants represent deprotonation either at sulphur or at nitrogen, and the macro-constant sum here is the acid dissociation constant 
  Similarly, a base such as spermine has more than one site where protonation can occur. For example, mono-protonation can occur at a terminal  group or at internal  groups. The K values for dissociation of spermine protonated at one or other of the sites are examples of micro-constants. They cannot be determined directly by means of pH, absorbance, fluorescence or NMR measurements; a measured K value is the sum of the K values for the micro-reactions.
  Nevertheless, the site of protonation is very important for biological function, so mathematical methods have been developed for the determination of micro-constants.
  When two reactants form a single product in parallel, the macro-constant  For example, the abovementioned equilibrium for spermine may be considered in terms of K values of two tautomeric conjugate acids, with macro-constant In this case  This is equivalent to the preceding expression since  is proportional to 
  When a reactant undergoes two reactions in series, the macro-constant for the combined reaction is the product of the micro-constant for the two steps. For example, the abovementioned cysteine zwitterion can lose two protons, one from sulphur and one from nitrogen, and the overall macro-constant for losing two protons is the product of two dissociation constants  This can also be written in terms of logarithmic constants as