Histidine (His, H)
Positively charged side chain, essential in the human diet
What is the charge of histidine at pH 7.4?
At pH 7.4, the pH of blood plasma, histidine carries a net charge of +0.02, and 95% of its molecules are the zwitterion, charge 0. Its imidazole side chain, pKR 6.00, carries a proton in 4% of molecules. Its isoelectric point is 7.59, from Lehninger’s pKa values of 1.82, 9.17 and 6.00.
Properties of histidine
| Three-letter code | His |
|---|---|
| One-letter code | H |
| Side-chain class (Lehninger) | Positively charged |
| Side-chain group | imidazole |
| Formula (uncharged form) | C₆H₉N₃O₂ |
| Molar mass | 155.16 g/mol |
| pK₁ (α-carboxyl) | 1.82 |
| pK₂ (α-amino) | 9.17 |
| pKR (side chain) | 6.00 |
| Isoelectric point (pI) | 7.59 |
| Configuration at Cα (L form) | S |
| Hydropathy (Kyte and Doolittle) | −3.2 |
| mRNA codons | CAU, CAC |
| Human diet | 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 histidine at common pH values
| pH | Net charge | Most common form | Share of molecules |
|---|---|---|---|
| 1 | +1.87 | dication (+2) | 87% |
| 3 | +1.06 | cation (+1) | 94% |
| 5 | +0.91 | cation (+1) | 91% |
| 7 | +0.08 | zwitterion (0) | 90% |
| 7.4 (blood plasma) | +0.02 | zwitterion (0) | 95% |
| 9 | −0.40 | zwitterion (0) | 60% |
| 11 | −0.99 | anion (−1) | 99% |
| 13 | −1.00 | anion (−1) | over 99.9% |
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 1.82: the dication, net charge +2.
- pH 1.82 to 6.00: the cation, net charge +1.
- pH 6.00 to 9.17: the zwitterion, net charge 0.
- Above pH 9.17: the anion, net charge −1.
Open histidine 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 histidine at pH 7.4
- α-carboxyl (pK₁ = 1.82): −1/(1 + 10^(1.82 − 7.4)) = −1.0000
- α-amino (pK₂ = 9.17): +1/(1 + 10^(7.4 − 9.17)) = +0.9833
- imidazole (pKR = 6.00): +1/(1 + 10^(7.4 − 6.00)) = +0.0383
- q = −1.0000 + 0.9833 + 0.0383 = +0.0216
- q ≈ +0.02
How to calculate the pI of histidine
Histidine has three ionizable groups. Taken from the lowest pKa up, its neutral form exists between pKR (6.00, the imidazole) and pK₂ (9.17, the α-amino), so the pI is the mean of those two.
Isoelectric point of histidine
- pI = (pKR + pK₂)/2
- = (6.00 + 9.17)/2
- = 7.585 ≈ 7.59
The two printed pKas average to 7.585, exactly halfway between 7.58 and 7.59; Lehninger’s table gives 7.59, the value used on this page.
Averaging all three pKas, a common mistake, gives 5.66, 1.93 pH units below the pI.
Stereochemistry
L-histidine 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 histidine compares with the other 19
- Histidine is one of 3 amino acids in the class Lehninger calls positively charged; the others are lysine and arginine.
- Its molar mass, 155.16 g/mol, makes it the 5th heaviest of the 20.
- Its pI, 7.59, is the 3rd highest of the 20.
- On Kyte and Doolittle’s hydropathy scale it scores −3.2, the 7th most hydrophilic of the 20.
- It has 2 codons, as do 8 of the other 19.
Is histidine an essential amino acid?
Yes. Histidine is one of the 9 essential amino acids, which the body cannot make from other molecules in the amounts it needs, so they have to come from food. The other 8 are isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine.
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 histidine
Histidine is encoded by 2 of the 61 sense codons in the standard genetic code: CAU and CAC in mRNA, written CAT and CAC 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 histidine
- Amino Acid 3D Explorer: histidine in 3D, with its charge at any pH
- Molar mass of C₆H₉N₃O₂, 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
- Histidine on Wikipedia