The simple average molecular weight of the 20 common amino...

The simple average molecular weight of the 20 common amino acids is $138,$ but most biochemists use 110 when estimating the number of amino acids in a protein of known molecular weight. Why do you suppose this is? (Hint: there are two contributing factors to the answer. One of them will be apparent from a brief consideration of the amino acid compositions of common proteins. See, for example, Figure 5.16 of this text.)

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Peptide Bond Formation and Water Loss

During the formation of peptide bonds, a water molecule is released for every bond that is formed. This condensation reaction means that the mass of each amino acid residue in the protein is actually less than the free amino acid mass. Therefore, while the simple average of free amino acids is about 138, when they are part of a polypeptide chain, the average residue shows a lower mass due to the loss of water, contributing to the use of 110 as the estimate.

Amino Acid Composition Bias

Proteins typically do not consist of an equal mixture of all 20 amino acids. Instead, many proteins are enriched in certain amino acids that are generally lighter than the overall average. This natural bias in amino acid composition results in a lower effective average molecular weight of amino acid residues within proteins, further justifying the approximation of 110 instead of 138 when estimating protein size.

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