Selectivity of commonly used pharmacological inhibitors for cystathionine β synthase ( CBS ) and cystathionine γ lyase ( CSE )
Open accessAbstract
BACKGROUND AND PURPOSE: Hydrogen sulfide (H₂S) is a signalling molecule that belongs to the gasotransmitter family. Two major sources for endogenous enzymatic production of H₂S are cystathionine β synthase (CBS) and cystathionine γ lyase (CSE). In the present study, we examined the selectivity of commonly used pharmacological inhibitors of H₂S biosynthesis towards CSE and CBS. EXPERIMENTAL APPROACH: To address this question, human CSE or CBS enzymes were expressed and purified from Escherichia coli as fusion proteins with GSH-S-transferase. After purification, the activity of the recombinant enzymes was tested using the methylene blue method. KEY RESULTS: β-Cyanoalanine (BCA) was more potent in inhibiting CSE than propargylglycine (PAG) (IC₅₀ 14 ± 0.2 μM vs. 40 ± 8 μM respectively). Similar to PAG, L-aminoethoxyvinylglycine (AVG) only inhibited CSE, but did so at much lower concentrations. On the other hand, aminooxyacetic acid (AOAA), a frequently used CBS inhibitor, was more potent in inhibiting CSE compared with BCA and PAG (IC₅₀ 1.1 ± 0.1 μM); the IC₅₀ for AOAA for inhibiting CBS was 8.5 ± 0.7 μM. In line with our biochemical observations, relaxation to L-cysteine was blocked by AOAA in aortic rings that lacked CBS expression. Trifluoroalanine and hydroxylamine, two compounds that have also been used to block H₂S biosynthesis, blocked the activity of CBS and CSE. Trifluoroalanine had a fourfold lower IC₅₀ for CBS versus CSE, while hydroxylamine was 60-fold more selective against CSE. CONCLUSIONS AND IMPLICATIONS: In conclusion, although PAG, AVG and BCA exhibit selectivity in inhibiting CSE versus CBS, no selective pharmacological CBS inhibitor is currently available.
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PAG is an inhibitor with selectivity for CSE, while CHH inhibits CBS and cysteine aminotransferase.
“PAG is an inhibitor with selectivity for the enzyme cystathione γ-lyase (CSE), while CHH inhibits cystathione β-synthase (CBS) and cysteine aminotransferase [53].”
From Cytoprotective Effects of Hydrogen Sulfide in Novel Rat Models of Non-Erosive Esophagitis (2014) · cites this paper as [53]
The Discussion (page not provided) states that PAG is selective for CSE over CBS. The Introduction mentions cysteine aminotransferase, but the passages found do not say that CHH inhibits it or CBS (searched: CHH, cysteine aminotransferase). (LLM, conf=0.87)
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- Huang S Chua JH Yew WS Sivaraman J Moore PK Tan CH Site-directed mutagenesis on human cystathionine-gamma-lyase reveals insights into the modulation of H2S production J Mol Biol 2010 396 708 718 19961860
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- Authors
- Asimakopoulou, A., Panopoulos, P., Chasapis, C. T., Coletta, C., Zhou, Z., Cirino, G., Giannis, A., Szabo, C., Spyroulias, G. A., & Papapetropoulos, A.
- Affiliations
- University of Patras (GR)
- The University of Texas Medical Branch at Galveston (US)
- National and Kapodistrian University of Athens (GR)
- University of Naples Federico II (IT)
- Leipzig University (DE)
- Department of Anesthesiology University of Texas Medical Branch Galveston TX USA
- Corresponding author
- Papapetropoulos, Andreas
- ORCID
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2013-05-27
- Volume
- 169
- Issue
- 4
- Pages
- 922-932
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC3687671
- OpenAlex
- W1674148475
- Cited by
- 393
- References
- 51
- Citations by year
- 2026: 15 · 2025: 23 · 2024: 21 · 2023: 31 · 2022: 34 · 2021: 39 · 2020: 39 · 2019: 30 · 2018: 24 · 2017: 36 · 2016: 29 · 2015: 37 · 2014: 29 · 2013: 6
- FWCI
- 15.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- British Journal of Pharmacology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association (7-12-BS-184)
- European Commission (EU-FP7, EU FP7 REGPOT, 285950)
- European Social Fund (CT-2011-285950)
- FP7 Research Potential of Convergence Regions (CT-2011-285950, 285950)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Rheumatology › Folate and B Vitamins Research
- Keywords
- cystathionine beta-synthase, cystathionine gamma-lyase, beta-cyanoalanine, propargylglycine, aminooxyacetic acid, hydroxylamine, aortic rings, gasotransmitters
- MeSH terms
- Alanine, Alkynes, Animals, Aorta, Thoracic, Cystathionine beta-Synthase, Cystathionine gamma-Lyase, Enzyme Inhibitors, Glutathione Transferase, Glycine, Humans, Hydrogen Sulfide, Kinetics, Nitric Oxide, Peptide Fragments, Recombinant Fusion Proteins, Vasodilation, Rats, Sprague-Dawley, Nitric Oxide Donors, Rats, In Vitro Techniques
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