They’re easy numbers to take for granted, so it’s a good exercise once in a while to remind ourselves what pH, pKa and pI stand for:

pH—the measure of acidity. It’s the negative logarithm of the proton concentration.

pKa—an association constant. It’s the negative logarithm of the ratio of dissociated acid and conjugated base, over the concentration of the associated chemical.

pI—called the “isoelectric point,” this is the pH at which a molecule has a net neutral charge.

Why mind the p?

The “p” stands for “negative logarithm,” and makes it a lot easier to read an enormous range of concentrations by turning them into positive numbers. So, a molar concentration of 10-7 protons is much easier to read as a pH of 7. It’s important to note that acidity can be relative; if you have a weak acid, say, acetic acid in water, acetic acid will donate a proton. However, if you add a stronger acid, like HCl, to the solution, acetic acid will start accepting protons from HCl, and act like a base.

While you can still calculate the pH of an acid or base by measuring the molar concentration and leafing through a logarithmic table, it’s a lot easier to just look it up online or calculate it.

The basics of acidity

pH (and the other measures, too) creates a way to rank how easily a chemical donates a proton. The more readily it does this, the more acidic the chemical is. Hence, every chemical and molecule has a more or less distinct dissociation/association constant, Ka, which is calculated according to the following formula:

[proton][conjugate base]/[associated chemical].

Take the negative log of this result, and you get your pKa. Strong acids, being adept at giving away protons, will tend to have highly dissociated protons and conjugate bases in solution, and therefore have a large Ka.

pI in organic molecules

The pI of a protein is determined by the aggregate pH (and therefore pKa) of every amino acid in the protein chain. Each amino acid has its own pKa (and pI), but can vary according to how many other amino acids are surrounding your target amino acid. Remember, acid behavior can be relative (this also shows us why protein structure is crucial to understanding its function!).

The pI for very simple proteins, like two amino acids, is just the average pKa for each amino acid. Complex proteins, however, are much more difficult to calculate a pI for. But calculating pI can be important; most proteins carry a slight negative charge at biologically active pH (7). Also, the pI is the point where the protein is least soluble in water (because it has no net charge); this can help determine which proteins are more soluble than others.