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Amino Acid Charge at Physiological pH

Understanding how amino acids carry charge at physiological pH is essential for grasping protein structure and function. Learn about pKa values, zwitterions, and isoelectric point calculations.

By Wikipept Community | 2 min read
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The Zwitterion Concept

At physiological pH (approximately 7.4), most amino acids exist as zwitterions — molecules that carry both a positive and negative charge but have a net charge of zero. The amino group (NH3+) carries a positive charge, while the carboxyl group (COO-) carries a negative charge.

Mnemonic: Think of “zwitter” as “twin” charges. Every zwitterion has a positive twin and a negative twin living in the same molecule.

pKa Values and Charge States

Each ionizable group in an amino acid has a pKa value, which represents the pH at which that group is 50 percent protonated and 50 percent deprotonated.

  • Carboxyl group pKa: Approximately 2.0 (deprotonated at pH 7, charge negative)
  • Amino group pKa: Approximately 9.5 (protonated at pH 7, charge positive)
  • Side chain pKa: Varies widely (e.g., aspartate 3.9, histidine 6.0, lysine 10.5)

Rule of thumb: When pH is below pKa, the group is protonated. When pH is above pKa, the group is deprotonated. This simple rule lets you calculate the charge state of any amino acid at any pH.

Net Charge Calculation

To find the net charge of an amino acid at a given pH, determine the charge of each ionizable group and sum them. For example, at pH 7:

  • Glycine: NH3+ (+1) and COO- (-1) equals net charge zero
  • Aspartate: NH3+ (+1), COO- (-1), and side chain COO- (-1) equals net charge negative one
  • Lysine: NH3+ (+1), COO- (-1), and side chain NH3+ (+1) equals net charge positive one

Isoelectric Point (pI)

The isoelectric point is the pH at which an amino acid has a net charge of zero. It is calculated by averaging the two pKa values that bracket the neutral species:

  • Neutral amino acids: pI equals (pKa1 plus pKa2) divided by 2
  • Acidic amino acids: Average the two lowest pKa values
  • Basic amino acids: Average the two highest pKa values

Why This Matters

Charge determines how amino acids interact with water, other molecules, and each other. It influences protein solubility, folding, and binding. Electrophoresis and ion exchange chromatography both exploit charge differences to separate proteins and peptides.