Cysteine (Cys, C)
Polar, uncharged side chain, conditionally essential in the human diet
What is the charge of cysteine at pH 7.4?
At pH 7.4, the pH of blood plasma, cysteine carries a net charge of −0.14, and 86% of its molecules are the zwitterion, charge 0. Its thiol side chain, pKR 8.18, has lost its proton in 14% of molecules. Its isoelectric point is 5.07, from Lehninger’s pKa values of 1.96, 10.28 and 8.18.
Properties of cysteine
| Three-letter code | Cys |
|---|---|
| One-letter code | C |
| Side-chain class (Lehninger) | Polar, uncharged |
| Side-chain group | thiol |
| Formula (uncharged form) | C₃H₇NO₂S |
| Molar mass | 121.15 g/mol |
| pK₁ (α-carboxyl) | 1.96 |
| pK₂ (α-amino) | 10.28 |
| pKR (side chain) | 8.18 |
| Isoelectric point (pI) | 5.07 |
| Configuration at Cα (L form) | R |
| Hydropathy (Kyte and Doolittle) | 2.5 |
| mRNA codons | UGU, UGC |
| 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 cysteine at common pH values
| pH | Net charge | Most common form | Share of molecules |
|---|---|---|---|
| 1 | +0.90 | cation (+1) | 90% |
| 3 | +0.08 | zwitterion (0) | 92% |
| 5 | 0.00 | zwitterion (0) | 99.8% |
| 7 | −0.06 | zwitterion (0) | 94% |
| 7.4 (blood plasma) | −0.14 | zwitterion (0) | 86% |
| 9 | −0.92 | anion (−1) | 83% |
| 11 | −1.84 | dianion (−2) | 84% |
| 13 | −2.00 | dianion (−2) | 99.8% |
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 1.96: the cation, net charge +1.
- pH 1.96 to 8.18: the zwitterion, net charge 0.
- pH 8.18 to 10.28: the anion, net charge −1.
- Above pH 10.28: the dianion, net charge −2.
Open cysteine 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 cysteine at pH 7.4
- α-carboxyl (pK₁ = 1.96): −1/(1 + 10^(1.96 − 7.4)) = −1.0000
- α-amino (pK₂ = 10.28): +1/(1 + 10^(7.4 − 10.28)) = +0.9987
- thiol (pKR = 8.18): −1/(1 + 10^(8.18 − 7.4)) = −0.1423
- q = −1.0000 + 0.9987 − 0.1423 = −0.1436
- q ≈ −0.14
How to calculate the pI of cysteine
Cysteine has three ionizable groups. Taken from the lowest pKa up, its neutral form exists between pK₁ (1.96, the α-carboxyl) and pKR (8.18, the thiol), so the pI is the mean of those two.
Isoelectric point of cysteine
- pI = (pK₁ + pKR)/2
- = (1.96 + 8.18)/2
- = 5.07
Averaging all three pKas, a common mistake, gives 6.81, 1.74 pH units above the pI.
Stereochemistry
L-cysteine is R at its α-carbon, the only one of the 19 chiral amino acids that is not S. The sulfur in its side chain outranks the carboxyl oxygens under the Cahn-Ingold-Prelog rules, so the letter changes while the shape matches every other L amino acid. The R and S Configuration Explorer ranks the groups on a stereocenter step by step.
How cysteine compares with the other 19
- Cysteine is one of 5 amino acids in the class Lehninger calls polar, uncharged; the others are serine, threonine, asparagine and glutamine.
- Its molar mass, 121.15 g/mol, makes it the 7th lightest of the 20.
- Its pI, 5.07, is the 3rd lowest of the 20.
- On Kyte and Doolittle’s hydropathy scale it scores 2.5, the 5th most hydrophobic of the 20.
- It has 2 codons, as do 8 of the other 19.
Is cysteine an essential amino acid?
Only conditionally. Cysteine 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. It is made from serine, with its sulfur taken from methionine, one of the essential nine. The other 5 are arginine, glutamine, glycine, proline 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 cysteine
Cysteine is encoded by 2 of the 61 sense codons in the standard genetic code: UGU and UGC in mRNA, written TGT and TGC 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 cysteine
- Amino Acid 3D Explorer: cysteine in 3D, with its charge at any pH
- Molar mass of C₃H₇NO₂S, 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
- Cysteine on Wikipedia