# Lysine carboxypeptidase
**Lysine carboxypeptidase** (EC 3.4.17.3), also known as **carboxypeptidase N** or **kininase I**, is a zinc-dependent metallocarboxypeptidase found in blood plasma that removes C-terminal basic amino acids from peptides and proteins, with a preference for lysine over arginine. Its principal physiological role is the inactivation of bradykinin and the complement anaphylatoxins, inflammatory peptides whose activity depends on an intact C-terminal basic residue.[1](https://enzyme.expasy.org/EC/3.4.17.3) • [2](https://www.ncbi.nlm.nih.gov/mesh/68001121)
| Key fact | Detail |
|---|---|
| Accepted name | Lysine carboxypeptidase, EC 3.4.17.3; CAS registry number 9013-89-2[3](https://iubmb.qmul.ac.uk/enzyme/EC3/4/17/3.html) |
| Reaction | Release of a C-terminal basic amino acid, preferentially lysine[1](https://enzyme.expasy.org/EC/3.4.17.3) |
| Location | A zinc enzyme found in blood plasma; inactivates bradykinin and anaphylatoxins there[3](https://iubmb.qmul.ac.uk/enzyme/EC3/4/17/3.html) |
| Protein family | Peptidase family M14, the carboxypeptidase A family[3](https://iubmb.qmul.ac.uk/enzyme/EC3/4/17/3.html) |
| Other names | Carboxypeptidase N, kininase I, anaphylatoxin inactivator, bradykininase, arginine carboxypeptidase, plasma carboxypeptidase B, creatine kinase conversion factor[3](https://iubmb.qmul.ac.uk/enzyme/EC3/4/17/3.html) |
| Nomenclature history | Created 1972 as EC 3.4.12.7, transferred 1978 to EC 3.4.17.3, modified 1989[4](https://www.enzyme-database.net/downloads/ec3.pdf) |
| Reference sequences | Human CBPN_HUMAN Q9JJN5; bovine CBPN_BOVIN P15169; mouse CBPN_MOUSE Q9EQV8; rat CBPN_RAT Q2KJ83[1](https://enzyme.expasy.org/EC/3.4.17.3) |
## Catalytic function
The enzyme hydrolyzes the peptide bond at the carboxyl terminus when the terminal residue is a basic amino acid, lysine or arginine, releasing the free amino acid. The accepted name reflects the measured preference for lysine over arginine.[1](https://enzyme.expasy.org/EC/3.4.17.3) Substrate structure beyond the terminal residue matters: for human carboxypeptidase N, the specificity constant \( k_{\mathrm{cat}}/K_{m} \) is only 0.7 μM−1min−1 for the dipeptide Bz-Gly-Lys but 60.3 μM−1min−1 for Bz-Ala-Lys, an approximately 86-fold difference showing that the penultimate residue contributes substantially to binding and catalysis.[5](https://pmc.ncbi.nlm.nih.gov/articles/PMC2679228/) Comparative work on human carboxypeptidases B and N reached the same conclusion, reporting enhanced affinity of benzoyl-alanyl substrates over benzoyl-glycyl substrates and attributing it to significant participation of the penultimate amino acid.[6](https://www.sciencedirect.com/science/article/abs/pii/0003986179902716)
## Physiological role
By clipping the C-terminal arginine or lysine from inflammatory peptides, the enzyme regulates biologically active mediators, including the complement anaphylatoxins and kinins such as bradykinin.[7](https://www.brenda-enzymes.org/enzyme.php?ecno=3.4.17.3) Removing that terminal basic residue abolishes the biological activity of these peptides, which is why the enzyme carries the functional names anaphylatoxin inactivator and bradykininase.[2](https://www.ncbi.nlm.nih.gov/mesh/68001121) Because it circulates constitutively in plasma as a component of the blood, it can be present in any tissue sample or cultured cell that contains serum.[8](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lysine-carboxypeptidase)
## Family context
Lysine carboxypeptidase belongs to peptidase family M14, the metallocarboxypeptidase family named for carboxypeptidase A.[3](https://iubmb.qmul.ac.uk/enzyme/EC3/4/17/3.html) Within this family, subfamily M14B has been described as the "regulatory" subfamily because its members activate or inactivate biological mediators and peptide hormones; lysine carboxypeptidase inactivates bradykinin and anaphylatoxins in blood plasma, while carboxypeptidase E processes bioactive peptides such as enkephalin.[8](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lysine-carboxypeptidase) This contrasts with the "digestive" subfamily M14A, whose pancreatic members carboxypeptidases A and B break down food proteins.[8](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lysine-carboxypeptidase)
## Distinguishing it from related enzymes
Several other arginine/lysine carboxypeptidases cleave the same substrates, and all are stimulated by cobalt, which replaces the zinc in the active center, so other properties are needed to tell them apart.[8](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lysine-carboxypeptidase)
- **Carboxypeptidase B** is a digestive enzyme found in the pancreas or digestive tract, so it rarely needs to be considered in plasma work.[8](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lysine-carboxypeptidase)
- **Carboxypeptidase H** has a pH optimum at acid pH (pH 5 to 6), whereas carboxypeptidases N and M are optimally active at neutral pH (pH 7); purified carboxypeptidase H is also completely inhibited by 10 μM p-chloromercuriphenyl sulfonate, which does not inhibit carboxypeptidases N and M.[8](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lysine-carboxypeptidase)
- **Carboxypeptidase U** (thrombin-activatable fibrinolysis inhibitor, EC 3.4.17.20) is a plasma proenzyme activated during clotting by thrombin or plasmin; its active form has activity similar to the more stable lysine carboxypeptidase except that it shows no preference for Lys over Arg.[9](https://www.brenda-enzymes.org/enzyme.php?OrganismID=2681&UniProtAcc=Q96IY4&ecno=3.4.17.20)
Competitive inhibitors also serve as probes. Guanidinoethylmercaptosuccinic acid (GEMSA) inhibits human carboxypeptidases B and N with \( K_{i} \) values of 0.5 and 1.0 × 10−6 M respectively, and the all-carbon analog guanidinopropylsuccinic acid gives similar values.[6](https://www.sciencedirect.com/science/article/abs/pii/0003986179902716) GEMSA has been used as a presumably specific inhibitor of carboxypeptidase H in enzymatic assays, but it is not specific for that enzyme, and its use in that manner can lead to erroneous conclusions.[8](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lysine-carboxypeptidase)
## Measurement
Because carboxypeptidase N is a regulator of inflammation in blood, its activity in serum is of analytical interest. A fast kinetic coupled enzymatic assay has been described for the sensitive measurement of carboxypeptidase N activity in serum samples.[10](https://pubmed.ncbi.nlm.nih.gov/16616057/) Assays for this class of enzymes generally employ N-terminally blocked dipeptide substrates containing a C-terminal arginine or lysine.[8](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lysine-carboxypeptidase)
## References
1. [ENZYME entry: EC 3.4.17.3 lysine carboxypeptidase, ExPASy](https://enzyme.expasy.org/EC/3.4.17.3)
2. [Lysine Carboxypeptidase, MeSH, NCBI](https://www.ncbi.nlm.nih.gov/mesh/68001121)
3. [EC 3.4.17.3, IUBMB Enzyme Nomenclature](https://iubmb.qmul.ac.uk/enzyme/EC3/4/17/3.html)
4. [The Enzyme List, class 3 (EC 3.4.17.3 entry)](https://www.enzyme-database.net/downloads/ec3.pdf)
5. [Structure and Function of Human Plasma Carboxypeptidase N, the Anaphylatoxin Inactivator, PMC](https://pmc.ncbi.nlm.nih.gov/articles/PMC2679228/)
6. [Comparative studies on human carboxypeptidases B and N, Archives of Biochemistry and Biophysics](https://www.sciencedirect.com/science/article/abs/pii/0003986179902716)
7. [Information on EC 3.4.17.3, BRENDA Enzyme Database](https://www.brenda-enzymes.org/enzyme.php?ecno=3.4.17.3)
8. [Lysine Carboxypeptidase, an overview, ScienceDirect Topics](https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/lysine-carboxypeptidase)
9. [Information on EC 3.4.17.20 carboxypeptidase U, BRENDA Enzyme Database](https://www.brenda-enzymes.org/enzyme.php?OrganismID=2681&UniProtAcc=Q96IY4&ecno=3.4.17.20)
10. [A rapid and sensitive assay for the quantitation of carboxypeptidase N, PubMed](https://pubmed.ncbi.nlm.nih.gov/16616057/)
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*Topic: Encyclopedia › Life and health › Biological foundations › Biochemistry and metabolism › Enzyme classes and activities › Proteolytic and peptidase enzymes › Peptidases by cleavage specificity › Carboxypeptidases › Regulatory metallocarboxypeptidases (M14 family)*
*Initially written Sep 17, 2026 · Reviewed: Oct 21, 2026 · Edited: Oct 15, 2026; Oct 21, 2026 · Last review: Oct 21, 2026*
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