Proline (Pro, P)
Nonpolar, aliphatic side chain, conditionally essential in the human diet
What is the charge of proline at pH 7.4?
At pH 7.4, the pH of blood plasma, proline carries a net charge of 0.00, and over 99.9% of its molecules are the zwitterion, charge 0. Its side chain does not ionize, so only the α-carboxyl and α-amino groups are charged, and their charges nearly cancel. Its isoelectric point is 6.48, from Lehninger’s pKa values of 1.99 and 10.96.
Properties of proline
| Three-letter code | Pro |
|---|---|
| One-letter code | P |
| Side-chain class (Lehninger) | Nonpolar, aliphatic |
| Side-chain group | pyrrolidine ring |
| Formula (uncharged form) | C₅H₉NO₂ |
| Molar mass | 115.13 g/mol |
| pK₁ (α-carboxyl) | 1.99 |
| pK₂ (α-amino) | 10.96 |
| pKR (side chain) | none, the side chain does not ionize |
| Isoelectric point (pI) | 6.48 |
| Configuration at Cα (L form) | S |
| Hydropathy (Kyte and Doolittle) | −1.6 |
| mRNA codons | CCU, CCC, CCA, CCG |
| Human diet | Conditionally essential |
pKa values and pI from Nelson and Cox, Lehninger Principles of Biochemistry, 7th edition, Table 3-1. Formula and molar mass from the wwPDB Chemical Component Dictionary and the IUPAC standard atomic weights; codons from NCBI translation table 1; hydropathy from Kyte and Doolittle (1982); diet from the Institute of Medicine, Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (2005), chapter 10.
The values are facts and free to use; this page’s selection and presentation are © 2026 ScienceQuest.
Charge of proline at common pH values
| pH | Net charge | Most common form | Share of molecules |
|---|---|---|---|
| 1 | +0.91 | cation (+1) | 91% |
| 3 | +0.09 | zwitterion (0) | 91% |
| 5 | 0.00 | zwitterion (0) | 99.9% |
| 7 | 0.00 | zwitterion (0) | over 99.9% |
| 7.4 (blood plasma) | 0.00 | zwitterion (0) | over 99.9% |
| 9 | −0.01 | zwitterion (0) | 99% |
| 11 | −0.52 | anion (−1) | 52% |
| 13 | −0.99 | anion (−1) | 99% |
The net charge is an average over all the molecules, so it can be a fraction; each molecule carries a whole number of charges, and the most common form is the one protonation state with the largest share.
Which form dominates between the pKas
- Below pH 1.99: the cation, net charge +1.
- pH 1.99 to 10.96: the zwitterion, net charge 0.
- Above pH 10.96: the anion, net charge −1.
Open proline in the Amino Acid 3D Explorer and drag the pH to watch each group gain and lose its proton, with every pKa and its pI marked on the pH slider.
How the charge at pH 7.4 is calculated
Each group is treated on its own with the Henderson-Hasselbalch equation. An acidic group adds
−1/(1 + 10^(pKa − pH)), the share of molecules in which it has lost its proton, and a basic group
adds +1/(1 + 10^(pH − pKa)), the share in which it holds one.
Net charge of proline at pH 7.4
- α-carboxyl (pK₁ = 1.99): −1/(1 + 10^(1.99 − 7.4)) = −1.0000
- α-amino (pK₂ = 10.96): +1/(1 + 10^(7.4 − 10.96)) = +0.9997
- q = −1.0000 + 0.9997 = −0.0003
- q ≈ 0.00
How to calculate the pI of proline
Proline has two ionizable groups, so its neutral form, the zwitterion, lies between them and the pI is the mean of pK₁ and pK₂.
Isoelectric point of proline
- pI = (pK₁ + pK₂)/2
- = (1.99 + 10.96)/2
- = 6.475 ≈ 6.48
The two printed pKas average to 6.475, exactly halfway between 6.47 and 6.48; Lehninger’s table gives 6.48, the value used on this page.
Stereochemistry
L-proline is S at its α-carbon, as 18 of the 19 chiral amino acids are: its amino group outranks its carboxyl, which outranks its side chain. The R and S Configuration Explorer ranks the groups on a stereocenter step by step.
How proline compares with the other 19
- Proline is one of 7 amino acids in the class Lehninger calls nonpolar, aliphatic; the others are glycine, alanine, valine, leucine, isoleucine and methionine.
- Its molar mass, 115.13 g/mol, makes it the 4th lightest of the 20.
- Its pI, 6.48, is the 4th highest of the 20.
- On Kyte and Doolittle’s hydropathy scale it scores −1.6, the 8th most hydrophilic of the 20.
- It has 4 codons, as do 4 of the other 19.
Is proline an essential amino acid?
Only conditionally. Proline is one of 6 conditionally essential amino acids: the body makes it, but needs it from food when its own synthesis cannot keep up with demand. The other 5 are arginine, cysteine, glutamine, glycine and tyrosine.
Classification from the Institute of Medicine, Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (2005), chapter 10, which calls the three lists indispensable, conditionally indispensable and dispensable.
Codons for proline
Proline is encoded by 4 of the 61 sense codons in the standard genetic code: CCU, CCC, CCA and CCG in mRNA, written CCT, CCC, CCA and CCG on the DNA coding strand.
The DNA to Protein Translator reads codons in a sequence of your own, and the Protein Synthesis Simulator builds the chain on a ribosome, one amino acid per codon.
Work with proline
- Amino Acid 3D Explorer: proline in 3D, with its charge at any pH
- Molar mass of C₅H₉NO₂, worked out atom by atom in the Molar Mass Calculator
- Henderson-Hasselbalch Calculator: the acid to base ratio of one group at any pH
- Titration Curve Calculator: the curve for a weak acid titrated with a strong base
- All 20 amino acids: pKa values, pI, charge and codons in one table
- Proline on Wikipedia